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Genetically Identical Twins and Different Disease Risk Essay

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Updated: Apr 7th, 2022

Introduction

Monozygotic (MZ) twins grow from the same single-cell zygote formed from the fusion of one egg and one sperm. In MZ twins, the inner cell mass of the blastocyst splits into two during the early cell divisions and gives rise to two embryos that are genetically identical. The study of MZ twins offers fascinating insights that help researchers explore the link between the sequence of the genotype and the phenotype (Carey, 2011). Although MZ are genetically identical, they may have different diseases at different times, a phenomenon called -twin discordance (Carey, 2011).

The purpose of this paper is to discuss how DNA differs in older and younger twin sets. The differences in disease risk during their lifespan will also be discussed. Finally, the implications of reducing disease risk will be addressed.

DNA differs in older twin sets than younger twin sets

Monozygotic twins are identical at the DNA sequence level but studies have found some phenotypic differences of DNA methylation and histone modification profiles that may be the results of different exposures to environmental stressors. This may affect their susceptibility to different diseases such as cancer or autoimmune disorders (Kaminsky et al., 2009; Fraga et al., 2005; Javierre et al., 2010).

There is a prevalent epigenetic drift in monozygotic twins as they advance in age (Fraga et al., 2005). Fraga et al. (2005) investigated both global and locus-specific differences in DNA methylation and histone acetylation in identical twins of various ages. Their results revealed that young identical twin pairs are essentially identical in their epigenetic markings while older identical twin pairs demonstrate significant variations in epigenetic differences in DNA methylation and histone modification. These differential markers between twins are distributed throughout their genomes, affecting repeat DNA sequences and single-copy genes, and have an impact on gene expression.

Interestingly, variations in gene expression in older twin pairs were four times greater than those observed in young twin pairs. They also found that that these epigenetic modifications were more distinctive in older MZ twins with different lifestyles and who had spent less of their lives together; this emphasized the significance of the role of environmental factors in translating a common genotype into a different phenotype.

In a subsequent study, Martin (2005) reported that epigenetic shifts in the aging identical twins could have arisen from endogenous stochastic mechanisms independent of environmental perturbations or could have resulted from such environmental perturbations. These results constitute the most detailed results of age-associated epigenetic alterations in MZ twins of human subjects.

In the same breath, Talens et al. (2012) conducted a study to investigate the occurrence of epigenetic changes over the adult lifespan in monozygotic twin pairs (N=230, 18-89 years). They examined the global DNA methylation differences and found that there was more variation within old MZ-pairs as compared to young pairs. Furthermore, elderly twins revealed a similar pattern of variations in DNA methylation after a 10 year follow-up.

They concluded that the age-related increase in methylation variation was generally related to the distinct environmental factors for which familial factors may play a more important role. In conclusion, sustained epigenetic differences arise from early adulthood to old age and contribute to an increasing epigenetic variation of MZ twins during aging (Talens et al., 2012)

It must be noted that discordance for numerous multifaceted diseases is not necessarily associated aging. Kaprio et al. (1992) studied the cumulative incidence, concordance rate, and heritability for diabetes mellitus in a nationwide cohort of 13,888 twin pairs of the same sex in Finland. They found that the concordance rate for Type 1 diabetes was higher among monozygotic than dizygotic in the first and second decades of life.

They concluded that heritability for Type 1 diabetes was greater than that for Type 2 where both genetic and environmental factors seemed to play a significant role. In a different study, Bergem et al. (1997) compared the relative importance of heredity and the environment in the development of Alzheimer’s disease and vascular dementia. They found that the concordance of Alzheimer’s disease could be as high as 83% at a later age.

Collectively, epigenetic changes are not restricted to the prenatal period. Monozygotic twins experience an epigenetic drift between each another with advancing age (Fraga et al., 2005). Differences in epigenetic modifications are influenced by decreasing amounts of time shared together and behavioral differences (Fraga et al., 2005). Additionally, MZ twins provide a unique model that explains how genetically identical twins exhibit differences. This model lends itself to future research that addresses the role of epigenetic modifications in the establishment of the phenotype (Petronis et al., 2003; Wong, Gottesman, and Petronis, 2005).

Differences in disease risk during life span

Discordance of diseases in MZ twins

Identification of genes predisposing their carriers to complex diseases is a much more complicated task than finding genes involved in simple mendelian diseases. The dynamic epigenetic mechanisms provide an alternative explanation for some of the features of complex diseases which include late onset, gender effects; parents of origin effect, discordance of MZ twins and fluctuation of symptoms in complex diseases (Petronis, 2001).

MZ twins share the same genotype because they are derived from the same zygote. However, monozygotic twins have several phenotypic differences that determine their susceptibility to diseases. Recent studies suggest that phenotypic discordance between monozygotic twins is, at least to some extent, due to epigenetic factors that change over the lifetime of a multi-cellular organism. Acute environmental factors are directly associated with epigenetic-dependent disease phenotypes. This is demonstrated by the increased CpG-island promoter hyper-methylation of tumor suppressor genes in the normal oral mucosa of smokers (Poulsen, Esteller, Vaag, and Fraga, 2007).

MZ twins who are discordant for disease are an excellent example of how genetically identical individuals can exhibit differences and represent a unique model for studying the contribution and role of environmental factors in disease development. Since monozygotic twins are genetically identical, they are considered ideal experimental models for studying the role of environmental factors as determinants of complex diseases and phenotypes (Poulsen, Esteller, Vaag, and Fraga, 2007).

Psychosis-associated environmental exposures may result in long-lasting epigenetic alterations that impact on the neurobiological processes involved in pathology (Rutten and Mill, 2009). Dempster et al. (2011) performed a genome-wide analysis of DNA methylation on peripheral blood DNA samples obtained from MZ twin pairs discordant for major psychosis. Their results revealed disease-associated DNA methylation differs between twins discordant for schizophrenia and bipolar disorder individually and together as a combined major psychosis group.

Pathway analysis of our top loci highlighted a significant enrichment of epigenetic changes in biological networks and pathways directly associated with psychiatric disorder and neuro-development. Their data provided further evidence to support the role of DNA methylation differences in mediating phenotypic differences between MZ twins and in the etiology of both schizophrenia and bipolar disorder (Dempster et al., 2011). The understanding of epigenetic modifications and their potential for reversibility is therefore crucial for clinical psychiatry and may lead to the development of novel and innovative solutions for prevention and/or intervention (Rutten and Mill, 2009).

Along the same line, Mastroeni, McKee, Grover, Rogers and Coleman (2009) examined DNA methylation of monozygotic twins discordant for Alzheimer’s disease. Interestingly, they found significantly reduced levels of DNA methylation in temporal neocortex neuronal nuclei of the AD twins. These findings are consistent with the hypothesis that epigenetic mechanisms may mediate, at the molecular level, the effects of life events on AD risks and provide, for the first time, a potential explanation for AD discordance despite genetic similarities (Mastroeni, McKee, Grover, Rogers, and Coleman, 2009).

It is thus obvious that MZ twin pairs share a virtually identical genome but often differ in their susceptibility to mental disorders (Petronis, 2006). There has been considerable interest in the DNA methylation changes in monozygotic twins who are discordant for mental disorders (McGowan and Szyf, 2010). An example of a mental disorder variation is the variation in DNA methylation observed between MZ twins discordant for schizophrenia and bipolar II disorder (Petronis et al., 2003; Kuratomi et al., 2007).

When taken together, the evidence of the differences in DNA methylation between MZ twins could contribute to the discordance of mental disorders. As mentioned earlier, epigenetic modifications were reported to increase with age in MZ twins. This validates the fact that the observed epigenetic alterations in discordant MZ twins is not merely related to the etiology of the disease, but also to the epigenetic drift addressed earlier (Fraga et al., 2005).

Although epigenetic marks are established early during development and differentiation, adaptations occur throughout life in response to intrinsic and environmental stimuli which also mediate different cancers. In other words, epigenetic changes are now known to play a key role in most kinds of cancer both in the early and late stages of the disease (Esteller, 2007). Heyn et al. (2013) investigated the levels of DNA methylation in the blood of 36 pairs of twins diagnosed with and without breast cancer.

They identified an epigenetic alteration of 403 differentially methylated CpG sites in the MZ twin who will develop breast cancer (but not in the healthy one) by using whole blood from 15 twin pairs discordant for breast cancer and high-resolution DNA methylation analysis. Additionally, they found DNA hyper-methylation of the promoter region in primary breast cancer tissues and cancer cell lines. They concluded that hyper-methylation of DOK7 occurs years before tumor diagnosis. Their results are suggestive of a powerful epigenetic blood-based biomarker’s role and enhance the knowledge regarding breast cancer pathogenesis. However, further research is needed to understand the exact function of the DOK7 gene that could lead to preventative treatment (Heyn et al., 2013).

Further, MZ twins discordant for Type 2 diabetes constitute an ideal model for studying environmental contributions to type 2 diabetic traits. Ribel-Madsen et al (2012) examined whether global DNA methylation differences exist in major glucose metabolic tissues by collecting skeletal muscle and subcutaneous adipose tissue biopsies from 53-80 year-old monozygotic twin pairs discordant for type 2 diabetes. Their study suggested that acquired DNA methylation changes in skeletal muscle or adipose tissue gene promoters were quantitatively smaller between Type 2 diabetic and non-diabetic twins (Ribel-Madsen et al., 2012).

Collectively, all the above-mentioned studies suggest evidence that environment can influence epigenetic modifications. The findings that MZ twins have similar epigenotypes during early years of life but exhibit remarkable differences in the content and distribution of 5-methylcytocine and acetylated histone provide strong evidence that the epigenotype is metastable and displays temporal variability (Fraga et al, 2005). It is likely that many environmental factors and stochastic events contribute to the variations in the epigenome and the differences found in the concordance rates of diseases between MZ twins (Anway, Cupp, Uzumcu & Skinner, 2005)

Environmental influences and epigenetics

Epigenetics refers to a variety of processes that affect gene expression that is independent of the actual DNA sequence. Most importantly, recent evidence demonstrates that epigenetic information is susceptible to change in response to environmental stimuli including behavior and stressful experiences (Mathews et al., 2011). Over the past two decades, the discordant MZ twin design has emerged as a powerful tool for detecting phenotype risk factors while controlling unknown confounders (Bell and Spector, 2011).

There are several examples of environmental factors that influence epigenetics such as chemical and pollutant exposure. Evidence from epidemiological studies indicates that there is a possible link between chemicals, pollutants and epigenetic alterations within global DNA methylation in the peripheral blood (Christensen et al., 2009; Langevin at al., 2011). Global methylation alterations were observed in humans exposed to benzene (Bollati et al., 2007), tobacco smoke (Breitling, Yang, Korn, Burwinkel & Brenner, 2011) and particulate air pollution (Yauk et al., 2009).

Furthermore, exposure to particulate air pollution has been related to lower blood DNA methylation and increased hospitalization and death from cardiovascular diseases (Baccarelli et al., 2009). Interestingly, since several tumor suppressor genes show increased promoter methylation in healthy lung cells of smokers, there is significant association between tobacco smoking and altered DNA methylation (Belinsky et al., 2002).

Additionally, Hopper and Seeman (1994) conducted a cross-sectional study of bone density at the lumbar spine and femoral neck and shaft in 41 pairs of female twins (21 MZ twin pairs), 27 to 73 years of age, who were discordant for at least 5 pack-years of smoking. They measured bone density by dual-photon absorptiometry. There results revealed that smoking was associated with higher serum concentrations in the follicle-stimulating hormones and luteinizing hormones and lower serum concentrations of parathyroid hormones.

Differences in spinal bone density between members of a pair were associated with differences in the serum concentrations of the parathyroid hormone, calcium and urinary pyridinoline excretion (a marker of bone resorption). These results suggest that women who smoke one pack of cigarettes a day throughout adulthood will have an average deficit of 5 to 10 percent in bone density during menopause and this will lead to an increased risk of bone fracture (Hopper and Seeman, 1994).

Taken together, epigenetic mechanisms elucidate the ability of certain chemical compounds to initiate biological perturbations that can lead to malignancy. This presents challenges and opens new avenues in public health (Stein, 2012).

Another identified environmental factor that influences the epigenetic modifications is the nutritional factor which emerges as an important player in the interaction between the environment and epigenetics. Dietary requirements have possible effects on DNA methylation and gene expression programming (Niculescu and Zeisel, 2002; Poirier, 2002). It is well known that DNA methylation influences the expression of some genes and depends upon the availability of methyl groups from S-adenosylmethionine (SAM). In this regard, dietary components could affect cellular signaling pathways that deliver chromatin-modifying enzymes to specific sequences (McGowan, Meaney and Szyf, 2008).

For instance, diets deficient in nutrients important for the epigenetic metabolism like folate, choline and methionine are related to DNA methalations alterations, development of mental disorders (McGowan, Meaney, and Szyf, 2008) and an increased risk of developing atherosclerosis, neurological disorders and birth defects (Poirier, 2002).

The role of diet as a contributing factor in controlling global DNA methylation status has been best illustrated in adult males suffering from uremia and undergoing hemodylasis. These patients experience hyper-homocysteinaemia due to low methionine content as a result of folate depletion. Researchers found that these patients have reduced global and locus-specific DNA methylation. This was reversed after the administration of high doses of folic acid (Ingrosso et al., 2003).

In another study, Williams et al. (2006) conducted a study to investigate the effect of moderate alcohol intake on bone mineral density and fracture risk in 46 pairs of monozygotic twins discordant for alcohol consumption while controlling genetic effects and other confounding variables. Their results revealed a positive association between alcohol consumption and bone mineral density. They concluded that moderate alcohol consumption is not harmful to bone health in women and may even be beneficial (Williams et al., 2006).

Another aspect related to environmental influences is obesity. Greenfield et al. (2004) examined the causality of the C-reactive protein (CRP) in heart disease and obesity by looking at the relationship between CRP, accurately measured body fat, lipids, apolipoproteins, blood pressure and environmental and behavioral factors that are independent of genetic influences in 194 healthy female twins. Results revealed that CRP was strongly related to total and central abdominal obesity, blood pressure and lipid levels that were independent of genetic influences on CRP and obesity. These relationships are likely to contribute significantly to prospective associations between CRP, type 2 diabetes and coronary events (Greenfield et al., 2004).

On the other hand, there is a significant association between epigenetics and aging. Several reports indicate that there is an age-dependent decrease of global DNA methylation and concurrent sight specific hyper-mythylation (Rampersaud, Kauwell, Hutson, Cerda & Bailey, 2000). Epigenetic modification can mediate environmental influences on gene expression; DNA hypo-methylation observed with aging can contribute to disease in the elderly.

A greater understanding of epigenetic mechanism provides extensive opportunities for identifying the genetic and environmental factors that contribute to disease risks (Foley et al., 2009). Furthermore, stress-induced epigenetic modification may emerge during aging. Amusingly; the DNA methylation alterations observed with aging appear to be similar to the DNA methylation alterations in cancer development (Esteller, 2008; Kulis and Esteller, 2010). There is a need for further exploration of the alterations in specific epigenetic alterations in aging MZ twin pairs to elucidate the effect of the environmental factors and epigenetic modifications mechanism, while controlling the genetic variables.

Finally, stress is one of the most important and significant players that bridge the environment to the genes through epigenetic modifications. Ample of evidence from animal stress models indicate that stressful life event results in epigenetic modification in the brain, further more reveal the plasticity of the epigenome across the lifespan. For instance, It is well established that depression commonly occurs in the aftermath of chronic stress (Sheline, Gado, & Kraemer, 2003), where chronic stress can confer enduring epigenetic modifications that contribute to depression (Tsankova et al., 2006).

Tsankova et al. (2006) found that chromatin remodeling of the BDNF gene in the hippocampus may contribute to stress-induced depression by altering neural plasticity. They administered chronic social defeat stress followed by chronic tricyclic antidepressant to mice. They analysed adaptations at the levels of gene expression and chromatin remodeling of five brain-derived neurotrophic factor (BDNF) in the hippocampus.

They found that mice displaying the depressive-like phenotype exhibit reductions in hippocampal BDNF gene expression that is accompanied by persistent histone modifications of the BDNF gene. While, chronic tricyclic antidepressant reversed this downregulation, it also increased histone acetylation at these promoters. This study emphasizes an important role for histone remodeling in the pathophysiology and treatment of depression and highlight the therapeutic potential for histone methylation and deacetylation inhibitors in depression (Tsankova et al., 2006).

This suggests that such epigenetic modification induced by stress may increase inflammatory mediators within the brain. Furthermore, research from animal models indicate that psychological stress triggered by stressful events induce a distinct GR-dependent histone modifications in mature dentate gyrus granule neurons in the hippocampus that may participate in the behavioral adaptation of the organism to this event (Bilang-Bleuel et al., 2005). These changed in the dentate gyrus result from chromatin remodeling.

Along the same lines, Hunter et al. (2009) examined the effects of stress, stress duration, corticosterone administration, and fluoxetine treatment on the levels of hippocampal histone modifications. They found that acute stress increased the levels of histone methylation in the dentate gyrus. Chronic restraint stress resulted in histone modification. This chromatin remodeling within hippocampus produced by stress enhances the knowledge regarding the interplay of stress and hippocampal gene expression, and reveal the outlines of a potential chromatin stress response that may be diminished or degraded by chronic stress

Another important aspect with stressful environment there is evident release of neuroendocrine stress hormones that signal epigenetic modification in the immune system. For example, Krukowski et al. (2011) evaluated epigenetic mechanisms that may underlie the effect of stress hormones specifically glucocorticoids on natural killer cells cells. They found glucocorticoids significantly dysregulated NK cell function through an epigenetic mechanism, modification of histone acetylation status. This epigenetic modification decreases the expression of effector proteins necessary immune function of the activity of NK cells (Krukowski et al., 2011).

These finding demonstrate that on o fthe MZ twins could experience epigenetic modifications triggered by stressful environment. There is little evaluation of stress and epigenetic modification in humans; however, preliminary evidence revealed that for individuals with posttraumatic stress disorder externally experienced traumatic event induces downstream alterations in immune function by reducing methylation levels of immune-related genes (Udin et al., 2010).

These results propose that traumatic event to trigger long-lasting epigenetic modification in immune function through brain-immune interactions. Thus, this could be further explored in MZ twins by controlling for genetic differences and investigating comparisons among MZ twin pairs. Taken together, the evidence are highlight the need for more research in stress models in human that relate to the effect of the environment and increases susceptibility to disease related to stress in vulnerable populations.

Additionally, the stress of low socio-economic status s associated with a shortened life expectancy and appears to have an impact on telomere length. Cherkas et al. (2006) tested the hypothesis that socio-economic status is associated with telomere attrition independent of known risk factors influencing the aging process in 1552 female MZ twins. They measured the rate of white-blood-cell telomere attrition as a biological indicator of human aging. Then, a discordant twin analysis was completes on a subset to verify findings, which revealed that WBC telomere length was highly variable but significantly shorter in lower socio-economic status groups (Cherkas et al., 2006).

Collectively, these results suggest that environmental factors can induce stable alterations of epigenetic modifications, providing a mechanism by which environmental factors may lead to long-term biological effect and disease. Further studies are required to determine the extent to which epigenetic modification are involved in gene-environment interaction sin human and how environmental influences may transduce into epigenetic modifications (Corpet & Almouzni, 2007).

Implications for reducing disease risk

Epigenetic modifications have replenished the interest in the interaction between the environment and the genome. Through this paper, results from numerous studies demonstrates that epigenetic modifications is influenced by the environment, however, a key feature that distinguishes epigenetic modifications from genetic changes is their reversible nature, which provide exciting implications for identification of a multitude of preventive and therapeutic interventions of a wide range of disorders across the lifespan while reinforcing the idea that our genes are not our destiny (Stein, 2012).

Further knowledge and understanding regarding epigenetic modifications using the MZ model will lead to identifying susceptibility for certain disease through categorizing molecular mechanisms that trigger periods of biological vulnerability. The good news is evidence show that epigenetic modifications are reversible; the supportive evidence addressed earlier opens a window for a variety of novel epigenetic-based interventions that could be implemented at periods of biological vulnerability to prevent the harmful effects of stress and decrease incidence of disease.

Identical twins are found to differ in gene expression because of changes in methylation caused by factors such as diet, chemicals in the environment and relational experiences during early development, including caregiverinfant interactions (Hochberg et al., 2011). The development of interventions will aid in adjusting the influences of the environment upon the genome while reversing and /or preventing epigenetic modifications in order to improve health and quality of life. Several behavioral implications, nutritional implications and pharmacological implications are identified in the sections for the potential of reducing the risk for disease over the lifespan.

First, there are several behavioral therapies that could be aimed to alleviate stress or other environmental factors. For example, exercise is one the behavioral implication that will result in weight loss and provide resistance to stress-induced chromatin remodeling within the dentate gyrus. In hase been shown in rats who were exposed to greater physical activity prior to stress exposure, exhibit resistance to stress-induced chromatin remodeling within the dentate gyrus (Bilang-Bleuel et al., 2005). These findings demonstrate that stress-related learning results in hippocampal chromatin remodeling, which may facilitate behavioral adaptation to environmental challenge. This opens a wide window for the exploration of other behavioral life-style changes that aid in the prevention or restoration of epigenetic modification (Mathews and Janusek, 2011)

The comparison of MZ twins suggests that external and/or internal factors influence in the phenotype by altering the pattern of epigenetic modifications and thus modulating the genetic information. Smoking and some nutritional factors may induce epigenetic changes that modify gene expression, leading to different phenotypes. For, example, Seddon J, George S, Rosner (2006) reported associations between AMD and cigarette smoking, fish consumption, and omega-3 and linoleic acid intake among MZ and DZ twins in this study population.

This study of twins provides evidence that cigarette smoking increases risk while fish consumption and omega-3 fatty acid intake reduce risk of age-related macular degeneration. In a subsequent study Seddon, Reynolds, Shah, and Rosner (2011) evaluated monozygotic twin pairs with discordant age-related macular degeneration phenotypes to assess associations between behavioral and nutritional factors. Heavier smoking in MZ twins was significantly related to advanced stage of age-related macular degeneration.

While, higher dietary vitamin D, betaine, or methionine intake in MZ twins was significantly associated with earlier stage of age-related macular degeneration. These results are suggestive of the fact that behavioral and nutritional factors are associated with epigenetic mechanisms involved in the etiology of age-related macular degeneration (Seddon, Reynolds, Shah, and Rosner, 2011)

Along the same lines, ample of evidence implicate that specific nutritional bioactive dietary components can induce alter epigenetic modificatios, specifically in DNA mythelation and histone modification (Hardy and tollefsbol, 2011). Intresingly, these display anticancer properties and may play a role in cancer prevention. Numerous studies suggest that a number of nutritional compounds have epigenetic targets in cancer cells.

Importantly, emerging evidence strongly suggests that consumption of dietary agents can alter normal epigenetic states as well as reverse abnormal gene activation or silencing. It is thus cleas that dietary factors influence the epigenome and could be used in combination with other cancer prevention and chemotherapeutic therapies (Hardy and tollefsbol, 2011). Nutrients involved in one-carbon metabolism, namely folate, vitamin B12, vitamin B6, riboflavin, methionine, choline and betaine, are involved in DNA methylation by regulating levels of the universal methyl donor S-adenosylmethionine and methyltransferase inhibitor S-adenosylhomocysteine (Park, Friso, & Choi, 2012).

While, other nutrients and bioactive food components such as retinoic acid, resveratrol, curcumin, sulforaphane and tea polyphenols can modulate epigenetic patterns by altering the levels of S-adenosylmethionine and S-adenosylhomocysteine or directing the enzymes that catalyse DNA methylation and histone modifications (Park, Friso, & Choi, 2012).

Furthermore, evidence implicate that excessive ethanol ingestion and folate deficiency are identified as risk factors for several cancers. It this clear that ethanol impedes the bioavailability of dietary folate and is known to inhibit select folate-dependent biochemical reactions. In animal models, chronic alcohol ingestion was shown to produce hypomethylation of DNA in the colonic mucosa, a constant feature of early colorectal neoplasia. In addition, alcohol may redirect the utilization of folate toward serine synthesis and thereby may interfere with a critical function of methylenetetrahydrofolate, thymidine synthesis. It is thus clear that there is a significant metabolic association between alcohol and folate metabolism that needs further investigation (Park, Friso, & Choi, 2012).

Park, Friso, & Choi (2012) emphesized that since aging and age-related diseases are associated with profound changes in epigenetic patterns, identification epigenetic pattern that facilitate healthy aging through nutritional measures is crucial.

Recent studies suggest that epigallocatechin-3-gallate (EGCG), which is the main polyphenolic constituent of green tea, may be used for the prevention and treatment of various neurodegenerative diseases by promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis (Wang, Li, Xu, Song, Tao, & Bai, 2012). These results are suggestive that EGCG may be beneficial to hippocampus-dependent learning and memory.

It is well established that epigenetic modifications is reversible, which makes modulation of epigenetic states a potential new therapeutic option for cancer and other disease (Corpet & Almouzni, 2007). A number of agents that alter patterns of DNA mythelation are being tested in clinical trail (Egger, Liang, Aparicio, and Jone, 2004), along with ongoing research for agents that can inhibit methyltranferases directly to target other epigenetic regulators (Corpet, A., & Almouzni, 2007).

There is a promising potential regarding the development of epigenetic therapies, which have shown hopeful anti-tumorigenic effects for some malignancies. These epigenetic therapies could include several inhibitors of enzymes controlling epigenetic modifications through DNA methyltransferases and histone deacetylases (Egger, Liang, Aparicio, and Jone, 2004). Finally, the development of more specific agents capable of targeting discrete brain regions is another fruitful area that await more research (Mathews and Janusek, 2011)

Conclusions

Evidence using the MZ twins has revealed that a difference in DNA methylation emerges later in life, suggesting an environmental rather than a genetic basis for the lifelong DNA methylation drift (Fraga et al., 2005).

Thus, it is possible that environmental exposures, which would affect the activity of the methylation machinery, would also lead to behavioral and mental pathologies. Future studies should now address the specific mechanisms responsible for the observed epigenetic drift of MZ twins. Such studies can provide key insight regarding the impact of environment-gene interaction on behavior and vulnerability to disease over the lifespan. In conclusion, it is likely that epigenetic patterns translate or at least contribute to the relationship between the environment and human health (Mathews and Janusek, 2011)

The study of epigenetic profiles in twins offers an excellent opportunity to understand the causes and consequences of epigenetic variation. The contribution of epigenetic variants to complex phenotypes can be assessed using disease-discordant MZ twins who are otherwise matched for genetics, age, sex, cohort effects, maternal effects and a common environment. These twin designs are considerably more powerful discovery tools than studies on singletons. In the near future, large-scale epigenetic studies in twins across different ages, tissues, and diseases will improve our understanding of the etiology and mechanisms of a wide range of common complex traits and diseases (Bell and Spector, 2011).

However, there are several limitations in regards to the investigation of how MZ twins are phenotypically different from one another. Researchers need to analyze hundreds of identical MZ twin pairs, control the manipulation of the environment, and obtain numerous samples of tissue and or genes at several time points across the lifespan. Additionally, researchers need to look at several generations of MZ twins. All thses limitations may not be feasible in human; therefore, laboratory animals could provide a venue to address complex research questions while controlling confounding variable of the environmental factors as much as possible (Carey, 2011)

References

Anway, M. D., Cupp, A. S., Uzumcu, M., & Skinner, M. K. (2005). Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility. Science, 308, 5727, 1466-1469.

Baccarelli, A., Wright, R. O., Bollati, V., Tarantini, L., Litonjua, A. A., Suh, H. H., Zanobetti, A.,… Schwartz, J. (2009). Rapid DNA methylation changes after exposure to traffic particles. American Journal of Respiratory and Critical Care Medicine, 179, 7, 572-8.

Ballestar, E. (2010). Epigenetics lessons from twins: prospects for autoimmune disease. Clinical Reviews in Allergy & Immunology, 39, 1, 30-41.

Belinsky, S. A., Palmisano, W. A., Gilliland, F. D., Crooks, L. A., Divine, K. K., Winters, S. A., Grimes, M. J.,… Crowell, R. E. (2002).Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Research, 62, 8, 2370-7.

Bell, J. T., & Spector, T. D. (2011). A twin approach to unraveling epigenetics. Trends in Genetics : Tig, 27, 3, 116-25.

Bergem, A. L., Engedal, K., & Kringlen, E. (1997). The role of heredity in late-onset Alzheimer disease and vascular dementia. A twin study. Archives of General Psychiatry, 54, 3, 264-70.

Bilang-Bleuel, A., Ulbricht, S., Chandramohan, Y., De, C. S., Droste, S. K., & Reul, J. M. (2005). Psychological stress increases histone H3 phosphorylation in adult dentate gyrus granule neurons: involvement in a glucocorticoid receptor-dependent behavioural response. The European Journal of Neuroscience, 22, 7, 1691-700.

Bollati, V., Baccarelli, A., Hou, L., Bonzini, M., Fustinoni, S., Cavallo, D., Byun, H. M.,… Yang, A. S. (2007). Changes in DNA methylation patterns in subjects exposed to low-dose benzene. Cancer Research, 67, 3, 876-80.

Breitling, L. P., Yang, R., Korn, B., Burwinkel, B., & Brenner, H. (2011). Tobacco-smoking-related differential DNA methylation: 27K discovery and replication. American Journal of Human Genetics, 88, 4, 450-7.

Carey, N. (2012). The epigenetics revolution: How modern biology is rewriting our understanding of genetics, disease, and inheritance. New York: Columbia University Press.

Champagne, F. A. (2008). Epigenetic mechanisms and the transgenerational effects of maternal care. Frontiers in Neuroendocrinology, 29, 3, 386-397.

Champagne, F. A., & Gene-Environment Interplay. (2012). Interplay Between Social Experiences and the Genome: Epigenetic Consequences for Behavior. Advances in Genetics, 77, 33-57.

Champagne, F. A., & Curley, J. P. (2011). Epigenetic influence of the social environment.

Champagne, F. A. (2011). Maternal imprints and the origins of variation. Hormones and Behavior, 60, 1, 4-11.

Champagne, F. A., & Mashoodh, R. (2009). Gene-environment interplay and the origins of individual differences in behavior. Current Directions in Psychological Science, 18, 3, 127-131.

Cherkas, L. F., Aviv, A., Valdes, A. M., Hunkin, J. L., Gardner, J. P., Surdulescu, G. L., Kimura, M.,… Spector, T. D. (2006). The effects of social status on biological aging as measured by white-blood-cell telomere length. Aging Cell, 5, 5, 361-365.

Christensen, B. C., Houseman, E. A., Marsit, C. J., Shichun, Z., Wrensch, M. R., Wiemels, J. L., Nelson, H. H.,… Kelsey, K. T. (2009). Aging and Environmental Exposures Alter Tissue-Specific DNA Methylation Dependent upon CpG Island Context. Plos Genetics, 5, 8.)

Corpet, A., & Almouzni, G. (2007). Epigenetics C. D. Allis, T. Jenuwein, D. Reinberg, Eds. Science New York Then Washington-, 316, 5828, 1126.

Csoka, A. B., & Szyf, M. (2009). Epigenetic side-effects of common pharmaceuticals: a potential new field in medicine and pharmacology.Medical Hypotheses, 73, 5, 770-80.

Dempster, E. L., Pidsley, R., Schalkwyk, L. C., Owens, S., Georgiades, A., Kane, F., Kalidindi, S.,… Mill, J. (2011). Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Human Molecular Genetics, 20, 24, 4786-96.

Dolinoy, D. C., & Jirtle, R. L. (2008). Environmental epigenomics in human health and disease. Environmental and Molecular Mutagenesis, 49, 1, 4-8.

Egger, G., Liang, G., Aparicio, A., & Jones, P. A. (2004). Epigenetics in human disease and prospects for epigenetic therapy. Nature, 429,6990, 457-63.

Esteller, M. (2008). Epigenetics in cancer. The New England Journal of Medicine, 358, 11, 1148-59.

Feil, R., & Fraga, M. F. (2012). Epigenetics and the environment: emerging patterns and implications. Nature Reviews Genetics.

Foley, D. L., Craig, J. M., Morley, R., Olsson, C. A., Dwyer, T., Smith, K., & Saffery, R. (2009). Prospects for epigenetic epidemiology.American Journal of Epidemiology, 169, 4, 389-400.

Fraga, M. F. (2005). From The Cover: Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences, 102, 30, 10604-10609.

Greenfield, J. R., Samaras, K., Jenkins, A. B., Kelly, P. J., Spector, T. D., Gallimore, J. R., Pepys, M. B.,… Campbell, L. V. (2004). Obesity is an important determinant of baseline serum C-reactive protein concentration in monozygotic twins, independent of genetic influences.Circulation, 109, 24, 3022-8.

Heyn, H., Carmona, F. J., Gomez, A., Ferreira, H. J., Bell, J. T., Sayols, S., Ward, K.,… Esteller, M. (2013). DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker. Carcinogenesis, 34, 1, 102-8.

Hochberg, Z., Feil, R., Constancia, M., Fraga, M., Junien, C., Carel, J. C., Boileau, P.,… Albertsson-Wikland, K. (2011). Child health, developmental plasticity, and epigenetic programming. Endocrine Reviews, 32, 2, 159-224.

Hopper, J. L., & Seeman, E. (1994). The bone density of female twins discordant for tobacco use. The New England Journal of Medicine,330, 6, 387-92.

Hunter, R. G., McCarthy, K. J., Milne, T. A., Pfaff, D. W., & McEwen, B. S. (2009). Regulation of hippocampal H3 histone methylation by acute and chronic stress. Proceedings of the National Academy of Sciences, 106, 49, 20912-20917.

Hunter, R. G., McCarthy, K. J., Milne, T. A., Pfaff, D. W., & McEwen, B. S. (2009). Regulation of hippocampal H3 histone methylation by acute and chronic stress. Proceedings of the National Academy of Sciences of the United States of America, 106, 49, 20912-7.

Ingrosso, D., Cimmino, A., Perna, A. F., Masella, L., De, S. N. G., De, B. M. L., Vacca, M.,… Zappia, V. (2003). Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia. Lancet, 361, 9370, 1693-9.

Javierre, B. M., Fernandez, A. F., Richter, J., Al-Shahrour, F., Martin-Subero, J. I., Rodriguez-Ubreva, J., Berdasco, M.,… Ballestar, E. (2010). Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Research, 20, 2, 170-9.

Kaminsky, Z. A., Tang, T., Wang, S. C., Ptak, C., Oh, G. H., Wong, A. H., Feldcamp, L. A.,… Petronis, A. (2009). DNA methylation profiles in monozygotic and dizygotic twins. Nature Genetics, 41, 2, 240-5.

Kaprio, J., Tuomilehto, J., Koskenvuo, M., Romanov, K., Reunanen, A., Eriksson, J., Stengård, J.,… Kesäniemi, Y. A. (1992). Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland.Diabetologia, 35, 11, 1060-7.

Krukowski, K., Eddy, J., Kosik, K. L., Konley, T., Janusek, L. W., & Mathews, H. L. (2011). Glucocorticoid dysregulation of natural killer cell function through epigenetic modification. Brain Behavior and Immunity, 25, 2, 239-249.

Kulis, M., & Esteller, M. (2010). DNA methylation and cancer. Advances in Genetics, 70, 27-56.

Langevin, S. M., Houseman, E. A., Christensen, B. C., Wiencke, J. K., Nelson, H. H., Karagas, M. R., Marsit, C. J.,… Kelsey, K. T. (2011).The influence of aging, environmental exposures and local sequence features on the variation of DNA methylation in blood. Epigenetics : Official Journal of the Dna Methylation Society, 6, 7, 908-19.

Lipman, T., & Tiedje, L. B. (2006). Epigenetic Differences Arise During the Lifetime of Monozygotic Twins. Mcn, the American Journal of Maternal/child Nursing, 31, 3.)

Martin, G. M. (2005). Epigenetic drift in aging identical twins. Proceedings of the National Academy of Sciences of the United States of America, 102, 30, 10413-4.

Mason, J. B., & Choi, S.-W. (2005). Effects of alcohol on folate metabolism: implications for carcinogenesis. Alcohol, 35, 3, 235-241.

Mathews, H. L., Konley, T., Kosik, K. L., Krukowski, K., Eddy, J., Albuquerque, K., Janusek, L. W.,… Special Issue: Adaptive Immunity in the Central Nervous System Function. (2011). Epigenetic patterns associated with the immune dysregulation that accompanies psychosocial distress. Brain Behavior and Immunity, 25, 5, 830-839.

Meaney, M. J., & Szyf, M. (2005). Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome. Dialogues in Clinical Neuroscience, 7, 2, 103-23.

Niculescu, M. D., & Zeisel, S. H. (2002). Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. The Journal of Nutrition, 132, 8.)

Park, L. K., Friso, S., & Choi, S. W. (2012). Nutritional influences on epigenetics and age-related disease. The Proceedings of the Nutrition Society, 71, 1, 75-83.

Petronis, A., Gottesman, I. I., Kan, P., Kennedy, J. L., Basile, V. S., Paterson, A. D., & Popendikyte, V. (2003). Monozygotic twins exhibit numerous epigenetic differences: clues to twin discordance?. Schizophrenia Bulletin, 29, 1, 169-78.

Petronis, A. (2006). Epigenetics and twins: three variations on the theme. Trends in Genetics : Tig, 22, 7, 347-50.

Petronis, A. (2001). Human morbid genetics revisited: relevance of epigenetics. Trends in Genetics : Tig, 17, 3, 142-6.

Petronis, A. (2001). Human morbid genetics revisited: relevance of epigenetics. Trends in Genetics, 17, 3, 142-146.

Poirier, L. A. (2002). The effects of diet, genetics and chemicals on toxicity and aberrant DNA methylation: an introduction. The Journal of Nutrition, 132, 8.)

Rampersaud, G. C., Kauwell, G. P., Hutson, A. D., Cerda, J. J., & Bailey, L. B. (2000). Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. The American Journal of Clinical Nutrition, 72, 4, 998-1003.

Ribel-Madsen, R., Fraga, M. F., Jacobsen, S., Bork-Jensen, J., Lara, E., Calvanese, V., Fernandez, A. F.,… Poulsen, P. (2012). Genome-Wide Analysis of DNA Methylation Differences in Muscle and Fat from Monozygotic Twins Discordant for Type 2 Diabetes. Plos One, 7,12.)

Rice, V. H. (2012). Handbook of stress, coping, and health: Implications for nursing research, theory, and practice. Thousand Oaks: SAGE Publications.

Seddon, J. M., George, S., & Rosner, B. (2006). Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: the US Twin Study of Age-Related Macular Degeneration. Archives of Ophthalmology, 124, 7, 995-1001.

Segman, R. H., Shefi, N., Goltser-Dubner, T., Friedman, N., Kaminski, N., & Shalev, A. Y. (2005). Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors. Molecular Psychiatry, 10, 5, 425.

Stein, R. A. (2012). Epigenetics and environmental exposures. Journal of Epidemiology and Community Health, 66, 1, 8-13.

Szyf, M. (2012). The early-life social environment and DNA methylation. Clinical Genetics, 81, 4, 341-9.

Szyf, M., & Epigenetic Control of Gene Expression. (2009). The early life environment and the epigenome. Bba – General Subjects,1790, 9, 878-885.

Szyf, M. (2007). The dynamic epigenome and its implications in toxicology. Toxicological Sciences : an Official Journal of the Society of Toxicology, 100, 1, 7-23.

Talens, R. P., Christensen, K., Putter, H., Willemsen, G., Christiansen, L., Kremer, D., Suchiman, H. E.,… Heijmans, B. T. (2012). Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs. Aging Cell, 11, 4, 694-703.

Trygve, O. T., & Tabitha, M. H. (2011). Epigenetic diet: impact on the epigenome and cancer. Epigenomics, 3, 4, 503-518.

Tsankova, N. M., Berton, O., Renthal, W., Kumar, A., Neve, R. L., & Nestler, E. J. (2006). Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nature Neuroscience, 9, 4, 519-25.

Uchida, S., Nishida, A., Hara, K., Kamemoto, T., Suetsugi, M., Fujimoto, M., Watanuki, T.,… Watanabe, Y. (2008). Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA-mediated down-regulation of the glucocorticoid receptor.The European Journal of Neuroscience, 27, 9, 2250-61.

Uddin, M., Aiello, A. E., Wildman, D. E., Koenen, K. C., Pawelec, G., de, L. S. R., Goldmann, E.,… Galea, S. (2010). Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proceedings of the National Academy of Sciences of the United States of America, 107, 20, 9470-5.

Unterberger, A., Szyf, M., Nathanielsz, P. W., & Cox, L. A. (2009). Organ and gestational age effects of maternal nutrient restriction on global methylation in fetal baboons. Journal of Medical Primatology, 38, 4, 219-27.

Wang, Y., Li, M., Xu, X., Song, M., Tao, H., & Bai, Y. (2012). Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis. Molecular Nutrition & Food Research, 56, 8, 1292-303.

Waterland, R. A., & Jirtle, R. L. (2003). Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Molecular and Cellular Biology, 23, 15, 5293-300.

Williams, F. M., Cherkas, L. F., Spector, T. D., & MacGregor, A. J. (2005). The effect of moderate alcohol consumption on bone mineral density: a study of female twins. Annals of the Rheumatic Diseases, 64, 2, 309-10.

Wong, A. H. C., Gottesman, I. I., & Petronis, A. (2005). Phenotypic differences in genetically identical organisms: the epigenetic perspective. Human Molecular Genetics, 14, 1, 11.

Yauk, C., Polyzos, A., Rowan-Carroll, A., Somers, C. M., Godschalk, R. W., Van, S. F. J., Berndt, M. L.,… Kovalchuk, O. (2008). Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location. Proceedings of the National Academy of Sciences, 105, 2, 605-610.

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