enome contains sites that are responsive to different extraneous signals that are particularly involved in nodal regulatory pathways, and is thus consistent with the view that the DNA methylome is adapted to signals from the environment.56 The fact that these variable sites were purchase Halofuginone common to many twin pairs and stable over time may mean that many of these changes occurred early in life and were then maintained throughout life. These kinds of DNA methylation changes are hypothesized to play a role in 
stable phenotypes that emerge in response to PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19835880 early life exposures. Another critical question is whether this putative process of DNA methylation variation is stable or dynamic over short periods of time. In the present twin study, those genes that were the most dynamic or unstable over time were associated with similar, albeit fewer, networks involved in organismal development and developmental disorders, cellular growth and proliferation, as well as cell signaling and different diseases. This provides support for the hypothesis that the DNA methylome is highly responsive in adolescence to experience and extraneous signals. It should be emphasized that the stable and dynamic sites identified in our study were likely a conservative estimate of such variation in adolescence, given the limited environmental variation within twin pairs. It stands to reason that the variation in DNA methylation would be larger in the general population given the wider range of environmental exposures and life course experiences. Nevertheless, the present study distinguished genetic-innate variations from others and thus established the plausibility of this hypothesis. In regards to hypervariable genes that were stable over time, it is of particular interest that we found multiple sites on several major histocompatibility complex genes, also known as the human leukocyte antigens in humans. These genes are involved in immune functions,57 and may be divided into 3 different classes. Among our hypervariable genes, we specifically found the HLA-C from Class I and the MHC complex II, HLA-DQA1, HLA-DQB1, HLA-DRB1, and HLA-DRB5 from Class II. All are implicated in presenting foreign antigens to the immune system.57 Other studies have found DNA methylation of such genes in association with gastric cancer and type 1 diabetes. Interestingly, Ye and colleagues58 found that HLA-C promoter methylation patterns were also associated with age and gender. The present twin study suggests that environmental epigenetic processes may drive some of the variation in HLA functions that are already associated with inter-individual differences in susceptibility to disease in adolescence. 1416 Epigenetics Volume 9 Issue 10 Remarkably, the HLA-DQB1 gene came up as both variable in a stable manner and responsive in adolescence, although different sites were associated with stability and variation in time. A member of the MHC Class II, HLA-DQB1 provides instructions for making a protein with a critical role for the immune system and assists the immune system in distinguishing foreign invaders from the body’s own proteins and has been involved in both celiac disease60 and narcolepsy,61 again pointing to putative epigenetic-environmental origins for some of these vulnerabilities. In addition to its strong design and the fact that this study had a very narrow age range specifically focused at the mid-adolescent period, a strength of this study is the assessment of variability in epigenetic patterns