for me and many other women "MS" is more prevalent in women and on the increase

 on Medscape

http://www.medscape.com/viewarticle/735434

HLA-DRB*15 is implicated

January 7, 2011 — Women with multiple sclerosis (MS) are more likely to have a human leukocyte antigen (HLA) gene variant associated with MS than men, report researchers. It is a finding that may explain the preponderance of disease among women. This gene region appears also to be the site of gene-environment interactions, the study authors suggest.

The new study appears in the January 5 issue of Neurology.

Research has shown that the number of people diagnosed as having MS has been rising, and the rate has been climbing faster among women than men.

The cause of MS is not known, but evidence suggests that it is triggered by environmental factors in people who are genetically susceptible to the disease. The main genetic contribution in MS comes from the major histocompatibility complex, the study authors note, more specifically the HLA class II genes.

In the current study, the researchers evaluated HLA genes of 1055 families with more than 1 person with MS.

Investigators tested the genes of 7093 people. Of these, 2127 had MS. The researchers evaluated the genes for people with and without the disease and examined whether those with MS inherited the susceptibility gene from their mother or their father and what the relationship was between people in the same family with MS.

Investigators found that women with MS were 1.4 times more likely to have the HLA gene variant associated with MS than men.

HLA-DRB1*15

A total of 919 women and 302 men had the risk allele HLA-DRB1*15. This compared to 626 women and 280 men who did not have the gene variant.

"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," senior investigator George Ebers, MD, from the University of Oxford in the United Kingdom, said in a news release.

In another recent study published by these same investigators, they saw a maternal parent-of-origin effect for the HLA-DRB1*15 allele only if mothers transmitted MS to their daughters but not to their sons (Hum Mol Genet. 2010;19:3679-3689). This result could explain the increased female-to-female over female-to-male or male-to-male inheritance of the disease in the same population.

How environment interacts with genes to affect MS risk is now under investigation, the study authors point out. "There are now 5 discrete insights relevant to this interaction, which include the maternal parent-of-origin effects, month-of-birth effects, presence of vitamin D responsiveness in a susceptibility gene, and transgenerational differences in allele frequency. Here, we add a fifth interaction with gender ratio," they add. "All of these localize to the major histocompatibility complex."

Important Observations

In an accompanying editorial, Orhun Kantarci, MD, from the Mayo Clinic in Rochester, Minnesota, applauds the study authors for making several important observations in this new study.

Women with MS are more likely to share HLA-DRB1*15 transmission with other women than men with the disease within the same nuclear family, Dr. Kantarci noted. "If the inheritance was purely genetic, women would always transmit HLA-DRB1*15 to their offspring with MS more than men would regardless of the gender of the offspring." He suggests that some other sex-related factors, possibly epigenetic, modify this inheritance pattern.

The new study also showed that second-degree relatives, such as aunts and nieces or nephews, were more likely to inherit the risk variant than first-degree relatives, such as siblings or parents and children.

"It appears that the less the genetic sharing between individuals, the higher the interaction is between female sex and inheritance of the HLA gene variant," Dr. Kantarci added in a news release. "These findings pave the way for future studies of these genes, hopefully to advance our understanding of inheritance of complex diseases such as multiple sclerosis."

This study was funded by the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Society of the United Kingdom. Dr. Ebers serves on the editorial boards of the International Multiple Sclerosis Journal and Multiple Sclerosis. He has received funding from Roche, UCB, and Bayer Schering Pharma. Editorialist Dr. Kantarci has received research support from the Multiple Sclerosis Society, the Mayo Foundation, and the Hilton Foundation.