NEWS: Genetic Variant May Explain Why Women Develop Multiple Sclerosis More Than Men

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Genetic Variant May Explain Why Women Develop Multiple Sclerosis More Than

Men

ROCHESTER, Minn. -- Why do women develop multiple sclerosis (MS) almost

twice as often as men? Physicians have long been intrigued by this fact --

and now a Mayo Clinic-led international research team has identified a

genetic variation that may explain it.

The report from collaborators in Minnesota, Northern Ireland, Belgium and

Italy appears in the Jan. 27 online publication of the journal Genes &

Immunity (http://www.nature.com/gene/).

Significance of the Finding

" In practical terms, this is what our findings suggest: How much of the

protein known as 'interferon gamma' you produce 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, " explains the study's lead author,

Mayo Clinic neurologist Weinshenker, M.D. " If you have a gene that

produces high levels of interferon gamma, it may predispose you to

developing MS. Under this scenario, men get MS less often because they have

a lower frequency of a gene variant that is related to higher secretion of

interferon gamma. "

To researchers looking for a cure for MS -- where currently there is none --

the finding is helpful for three main reasons: 1) it provides a target at

which to direct future investigations into ways to stop MS, 2) it provides

leads on ways to improve treatments that can minimize the tissue and nerve

damage the disease causes, and 3) it may advance the search for new

treatments for other diseases. Notes Dr. Weinshenker, " Our finding isn't the

whole genetic cause, but it's a helpful step that could lead us to a more

complete understanding of MS -- and ultimately, effective treatment. It's

also a very promising lead about gender differences that may pertain to

susceptibility of other diseases, too, such as rheumatoid arthritis. "

About MS

MS is a complex neurological disease of the covering of the brain and spinal

cord that disrupts nerve transmission. It is caused by a combination of

genetic factors -- there is not a single MS gene -- and is also believed to

be influenced by various factors in the environment. MS is diagnosed in an

estimated 400,000 people a year in the United States, according to the

National Multiple Sclerosis Society (http://www.nationalmssociety.org).

The hallmark of the disease is the emergence of multiple areas of

inflammation and scarring of the protective myelin sheath that covers nerve

fibers. Symptoms include fatigue, weakness, balance problems, numbness and

vision problems if the optic nerve is affected. Though it often evolves into

a progressive disease, its severity varies widely. Some patients have few

discernable symptoms, while others steadily lose mobility and may require

wheelchair assistance to move.

The Mayo Clinic research group considers MS to belong to a group of diseases

known as autoimmune diseases, in which the body erroneously attacks its

healthy cells as if they were disease-causing foreign invaders. With MS, the

body attacks tissues of the brain and spinal cord, creating scars that

impair nerve signal transmission and lead to disability.

Background Biology

Interferon gamma belongs to a group of proteins that communicate with cells.

Research by scientists at the Cleveland Clinic has shown that women and men

naturally express different levels of interferon gamma. Experiments

elsewhere showed that high levels of interferon gamma could intensify the MS

damage processes and make the disease worse.

Combining these three lines of evidence -- 1) women get MS more often, 2)

women have higher levels of interferon gamma and 3) high levels of

interferon gamma worsen MS -- suggested to the Mayo Clinic research group

that interferon gamma may play a role in driving the gender bias toward

women in MS susceptibility. This would be especially true, they

hypothesized, if a genetic variant existed that produced high levels of a

kind of interferon gamma that tended to promote inflammation and tissue

damage, the hallmarks of MS. If that variant were overrepresented in women

compared to men, it would explain at least some of the excess risk of MS in

women. Through sophisticated genetic analysis, this is exactly what the

researchers found in the laboratory.

Then, in collaboration with researchers from Northern Ireland, Belgium and

Italy, the Mayo Clinic group compared MS in four patient populations. They

found that men have the gene variant that causes high levels of interferon

gamma less often than women. Says Dr. Weinshenker, " It seems as if men have

a lower frequency of high secretion interferon gamma genetic variant, and

that might explain why men are generally protected more from MS. "

Collaboration and Support

In addition to Dr. Weinshenker, research team members from Mayo Clinic

include: Orhun Kantarci, M.D.; Hebrink; Janet Schaefer-Klein; Mariza

de Andrade, Ph.D.; Atkinson; Sara Achenbach; and McMurray,

Ph.D. Other researchers include Koen Vandenbroeck, Ph.D.; Colin Graham,

M.D.; Stanley Hawkins, M.D.; and Shirley Haggerty from Belfast, Northern

Ireland; An Goris from the University of Leuven, Belgium; and Marrosu

from University of Caligari, Italy. Grants from the National Institutes of

Health and from the National Multiple Sclerosis Society supported the work.

http://www.sciencedaily.com/releases/2005/01/050128224022.htm