title: Complex disease, gender and epigenetics.
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.
authors: The Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Canada.
authors: Zachary
authors: Z
authors: Kaminsky
authors: Sun-Chong
authors: SC
authors: Wang
authors: Arturas
authors: A
authors: Petronis
mesh_terms: D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D012739:Gonadal Steroid Hormones / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012727:Sex Characteristics
chemical_list: D012739:Gonadal Steroid Hormones