Reporting on a study tracing MS in 1,055 families, investigators suggest that a gene long known to have association to MS susceptibility (HLA-DRB1*15) may be more likely to be found in women with the disease than men, and that women with this gene variation may be more likely to transmit it to other women in their families than to men. If confirmed by other investigators, the findings might help explain why women are more likely than men to develop MS, and reinforce the idea that factors other than genes, such as the environment, influence whether a person develops MS. Drs. Michael Chao, George Ebers and colleagues (University of Oxford, U.K.) report their findings in the January 5, 2011, online issue of (Neurology). The study was supported by the MS Society of Canada and the MS Society of Great Britain and Northern Ireland.
Background: While the cause of MS is still not known, scientists believe that a combination of several factors may be involved. While MS is not directly inherited, genes are known to make people susceptible to developing the disease. Studies are ongoing in the areas of genetics, immunology (the science of the body’s immune system) and epidemiology (who gets MS) in an effort to answer this important question.
Understanding the genetics of MS involves a multifaceted approach. One part of the effort to understand the genetic underpinnings of MS is genome analysis, involving the scanning of all genes in the body to find “hot spots” of gene activity relevant to MS. A dozen or so gene variations have been confirmed as being linked to MS susceptibility. Currently the International MS Genetics Consortium is completing the largest scan ever – with funding from the Wellcome Trust, the National MS Society and other agencies – which should identify all common genetic variations that play roles in MS susceptibility.
As MS susceptibility genes are identified, they provide possible clues to how MS is triggered, and possible ways to block those pathways to prevent the disease.
Another approach to studying MS genes involves focusing on the activity of these specific genes in groups of people with MS. In the current study, the genes under study are part of the MHC or “major histocompatibility complex,” which helps determine immune responses. MHC genes – particularly the gene HLA-DRB1*15 – have been linked to MS susceptibility.
Epidemiologic studies have revealed that MS affects women two to three times more often than men. Some research also suggests that this preponderance of women with MS may be growing, at least in some regions. Exploring gender differences is yielding new insight into the course of MS and possible therapeutic strategies involving sex hormones. In the current study, the authors were seeking to determine if the gender bias in MS is influenced by MHC genes.
The Study: The team examined the MHC genes of 1,055 families with more than one person with MS. In all, they tested the genes of 7,093 people, including 2,127 people with MS. The researchers looked at what MHC genes were active in people with and without MS, whether people with MS inherited the genes from their mother or their father, and what the relationship was between people in the same family with MS.
In this analysis, the authors found that women with MS might be more likely to have the HLA-DRB1*15 gene than men with MS. They also reported that women with this genetic variation were more likely to transmit it to other women in their families than to men. The authors suggest that their findings may help account for why women are more likely to develop MS than men.
Comment: If these results are confirmed by other investigators, they indicate an association between the gender bias in MS and genes, writes Orhun H. Kantarci, MD (Mayo Clinic, Rochester, MN) in an accompanying editorial. He notes that the findings lend evidence to the existence of “epigenetic” factors in the development of MS. Epigenetic factors are changes in how a gene functions that can be inherited, but are separate from the DNA itself, and can be influenced by environmental factors. This is a growing area of interest in MS genetics.
Read more about the search for MS genes.
Read more about gender differences.