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Researchers Find Clue to Why Women Get MS More Often Than Men

An international team of researchers funded in part by the National MS Society has uncovered a genetic clue which, if confirmed, may help explain why women develop MS about twice as often as men. The report, from collaborators in Minnesota, Northern Ireland, Belgium and Italy, appears in the Jan. 27 online publication of the journal Genes & Immunity.

It is known that genes play a part in making people susceptible to developing multiple sclerosis. There appear to be many separate genes that contribute to susceptibility. The international team, headed by Brian Weinshenker, MD (Mayo Clinic, Rochester, MN) has identified a variation in a gene that controls a powerful immune messenger chemical called interferon (IFN) gamma. Unlike interferon betas, which are used to treat MS, IFN gamma has been linked to immune attacks in MS, and recent evidence suggests that it is more active in women who have MS than in men.

The team compared MS in different U.S. and European populations. Their preliminary findings suggest that men have the gene variant that causes high levels of interferon gamma less often than women. This may explain why fewer men have MS than women. Dr. Weinshenker explains, “…Interferon gamma…appears to be a new key variable in understanding who gets MS and who doesn’t, and especially why women develop MS more often than men. If you have a gene that produces high levels of interferon gamma, it may predispose you to developing MS.”

The genetic variation identified by this international team may be just one piece of a complex puzzle. This finding, if confirmed, provides a possible target for further investigation into what causes MS and how to stop the immune-mediated disease.

This project was funded through collaborative funding between the National MS Society and the NIH's National Institute of Neurological Disorders and Stroke, as well as the National Institute of Allergy and Infectious Disease, to foster the study of the influence of gender on immune responses. Read more about progress resulting from that initiative.

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis.

Interferon-gamma (IFNgamma) treatment is deleterious in multiple sclerosis (MS). MS occurs twice as frequently in women as in men. IFNgamma expression varies by gender. We studied a population-based sample of US MS patients and ethnicity-matched controls and independent Northern Irish and Belgian hospital-based patients and controls for association with MS, stratified by gender, of an intron 1 microsatellite [I1(761)*CA(n)], a single nucleotide polymorphism 3' of IFNG [3'(325)*G --> A] and three flanking microsatellite markers spanning a 118 kb region around IFNG. Men carriers of the 3'(325)*A allele have increased susceptibility to MS compared to noncarriers in the USA (P=0.044; OR: 2.58, 95% CI: 0.97-8.08) and Northern Ireland (P=0.019; OR: 2.37, 95% CI: 1.10-5.13). There is a nonsignificant trend in the same direction in Belgian men (P=0.299; OR: 1.50, 95% CI: 0.71-3.26). Men carriers of I1(761)*CA(13), which is in strong linkage disequilibrium with the 3'(325)*A, have increased susceptibility (P=0.050; OR: 2.22, 95% CI: 0.98-5.40), while men carriers of I1(761)*CA(12) have decreased susceptibility (P=0.022; OR: 0.46, 95% CI: 0.23-0.90) to MS in the USA. Similar associations were reported in Sardinia between the I1(761)*CA(12) allele and reduced risk of MS in men. Flanking markers were not associated with MS susceptibility. Polymorphisms of IFNG may contribute to differences in susceptibility to MS between men and women.Genes and Immunity advance online publication, 27 January 2005; doi:10.1038/sj.gene.6364164.