Complex disease, gender and epigenetics

Zachary Kaminsky, Sun Chong Wang, Arturas Petronis

Research output: Contribution to journalReview articlepeer-review

173 Scopus citations


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
Pages (from-to)530-544
Number of pages15
JournalAnnals of Medicine
Issue number8
StatePublished - Dec 2006


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


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