Journal
ANNALS OF MEDICINE
Volume 38, Issue 8, Pages 530-544Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/07853890600989211
Keywords
chromatin; DNA methylation; epigenetics; epigenomic profiling; histones; hormone; microarrays; sexual dimorphism
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Funding
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH074127] Funding Source: NIH RePORTER
- NIMH NIH HHS [R01 MH074127-01] Funding Source: Medline
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Gender differences in susceptibility to complex disease such as asthma, diabetes, lupus, autism and major depression, among numerous other disorders, represent one of the hallmarks of non-Mendelian biology. It has been generally accepted that endocrinological differences are involved in the sexual dimorphism of complex disease; however, specific molecular mechanisms of such hormonal effects have not been elucidated yet. This paper will review evidence that sex hormone action may be mediated via gene-specific epigenetic modifications of DNA and histones. The epigenetic modifications can explain sex effects at DNA sequence polymorphisms and haplotypes identified in gender-stratified genetic linkage and association studies. Hormone-induced DNA methylation and histone modification changes at specific gene regulatory regions may increase or reduce the risk of a disease. The epigenetic interpretation of sexual dimorphism fits well into the epigenetic theory of complex disease, which argues for the primary pathogenic role of inherited and/or acquired epigenetic misregulation rather than DNA sequence variation. The new experimental strategies, especially the high throughput microarray-based epigenetic profiling, can be used for testing the epigenetic hypothesis of gender effects in complex diseases.
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