DNA Plus Environmental Factors Affect Women's Susceptibility to Multiple Sclerosis
Women have a greater risk of developing multiple sclerosis, but the reasons as to why this occurs has eluded scientists. The genetic predisposition is not found on the X chromosome as with other female-predominated conditions and 100 years ago, men and women were affected equally. Researchers with John Radcliffe Hospital in Oxford, though, have found another gene that may combine with environmental influences to affect a woman’s susceptibility to MS.
MHC Gene Plays Role in Many Autoimmune Diseases
George C. Ebers MD FMedSci and colleagues conducted a genomic analysis of more than 7,000 members of 1,055 families affected by MS. Of the more than 2,000 diagnosed with the condition, 73% were female.
The researchers focused on MHC (major histocompatibility complex) genes which play an important role in the immune system and autoimmunity. MHC genes are believed to be strongly associated with MS risk as well as being the primary genetic driver of other autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis.
The best known genes in the MHC region are referred to as human leukocyte antigen (HLA) genes which encode antigen-presenting proteins on the cell surface.
In families where a female was affected by MS, the families more often had the HLA-DRB1*15 genotype. HLA-DRB1 is a gene that plays a central role in the immune system by presenting peptides derived from extracellular proteins.
"Our findings also show women with the HLA gene variant are more likely to transmit the gene variant to other women in their families than to men," adds Dr. Ebers.
Genetics doesn’t likely explain the entire picture, points out Orhun Kantarci MD of the Mayo Clinic who writes in an accompanying editorial to the study published in the journal Neurology. “There does not seem to be enough evolutionary time to spread a purely genetic risk, and therefore [genomic-environmental interaction] seems to be the more likely explanation,” he writes.
The theory is that certain environmental factors such as diet, smoking, or stress may not affect a person without the gene mutation but trigger MS in people who are genetically susceptible. An earlier study by Dr. Ebers has suggested that vitamin D deficiency may be one environmental stressor that triggers the MS-linked gene alteration.
Chao M, et al "MHC transmission: Insights into gender bias in MS susceptibility" Neurology2011; 76: 242–46.
Kantarci O, "Sex-stratified inheritance of MS: New horizons from studies in MHC region"Neurology 2011; 76: 210-12.