Complex disease, gender and epigenetics

Zachary Kaminsky, Sun Chong Wang, Arturas Petronis

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)530-544
Number of pages15
JournalAnnals of Medicine
Volume38
Issue number8
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

Keywords

  • Chromatin
  • DNA methylation
  • Epigenetics
  • Epigenomic profiling
  • Histones
  • Hormone
  • Microarrays
  • Sexual dimorphism

ASJC Scopus subject areas

  • Medicine(all)

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