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Genetic association of multiple sclerosis and HL-A determinants

From the Neuroepidemiology and Genetics Unit, Department of Neurology, University of Minnesota, the Minneapolis Veterans Administration Hospital (Dr. Alter and Ms. Harshe); the Dight Institute, University of Minnesota (Dr. Anderson); and the Department of Laboratory Medicine and Pathology, University of Minnesota Hospitals, Minneapolis, Minnesota (Ms. Emme and Dr. Yunis).

Segregation of HL-A haplotypes was analyzed in 10 families in which there were at least two cases of multiple sclerosis. In nine families, multiple sclerosis was associated with only one parental HL-A haplotype. Specific HL-A determinants associated with multiple sclerosis differed among the families, suggesting that another histocompatibility-linked factor, possibly a gene determining susceptibility (or lack of resistance) played an etiologic role. Lod score analysis based on nine families suggested a close association between such a gene (labeled MSS) and the HL-A gene complex. However, when all 10 available families were analyzed, the association approached but did not reach statistical significance. Thus, the HL-A haplotype segregation did not prove that a histocompatibility-linked gene is related to the cause of multiple sclerosis, but study of additional multiplex families is certainly warranted. Other factors, possibly genetic (although not HL-A-linked), environmental, or the two together, may be required for multiple sclerosis to become clinically apparent.

Reprint requests should be addressed to Milton Alter. M.D. Chief, Neurology Service, Minneapolis Veterans Administration Hospital, 54th Street and 48th Avenue South, Minneapolis, MN 55417.

This work was supported in part by the graduate school, University of Minnesota; U.S.P.H.S. grant No. 2P01-HL06314-13; and the Minneapolis Veterans Administration Hospital.

Received for publication June 9, 1975.