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More MS news articles for July 2003

Possible interaction of CTLA-4 and HLA-DR15 in MS

July 7, 2003
Boston Cure Project

Cytotoxic T lymphocyte-associated antigen 4, or CTLA-4, is a protein that helps regulate T cell function and is considered a candidate genetic risk factor for MS. Genetic studies have given mixed results, however, with some finding an association between CTLA-4 variations and MS and others not finding any such association.

A new study published in the Annals of Neurology weighs in on the side of CTLA-4 being a genetic risk factor. This study examined a location on the CTLA-4 gene not yet investigated in MS, and found that one of the variations at this location tended to be found more often than expected in people with MS. The researchers then characterized the MS subjects for HLA-DR15 (another T cell related gene) status and found the CTLA-4 association only in those subjects who were DR15-positive. This analysis involved subjects from France; a follow-up study with people from Italy and Portugal found an association for CTLA-4 in both HLA-DR15 positive and negative groups, although the association in DR15-positive subjects was a little stronger. The CTLA-4 variation studied is located in the promoter region of the gene which controls how much CTLA-4 is made. It is not yet known what specific effect this variation actually has -- whether it increases or decreases production of CTLA-4, for instance. Further studies will need to be performed to confirm the results of this study, and to determine the actual biological effect of this variation.

While this study only sheds a little light on the genetic basis for MS, it illustrates a couple of methods currently being used in MS genetic studies. First, most MS scientists accept that MS is probably determined by common variations of multiple genes (as opposed to rare mutations in single genes), and therefore looking at individual genes may not reveal very much. Many of the studies being conducted today analyze two or more genes simultaneously, usually HLA-DR15 and some other gene of interest. Even better, as genetic studies become cheaper to conduct and data mining technology is more available, it should be possible to create databases containing information on thousands of genes from hundreds or thousands of subjects and let the computer find the sets of genes that together influence MS risk. Second, it seems very likely that MS genes differ from one population to another, and therefore scientists need to study a gene in many different populations to get a full picture of its contribution to MS. Hopefully the trend for future studies will be away from the "single-gene, single-population" type of study and toward the types of studies more likely to detect complex interactions of multiple genes.

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