Genetics

The most intensively studied genetic associations of multiple sclerosis are those within the human leukocyte antigen (HLA) region of the sixth chromosome. The most frequent association in Caucasoid populations is with HLA-DR2, though others, including DQwl, have been reported. The strength of the associations varies in different population groups. R. J. Swingler and D. A. S. Compston (1986), though cautious in interpreting their data, have reported that in the United Kingdom the north-south gradient of prevalence of multiple sclerosis is mirrored by a similar gradient in the frequency of DR2 in the control population. In the New World, G. C. Ebers and D. Bulman (1986) have shown that in the United States the areas of highest prevalence correspond with the areas of immigration from Finland and Scandinavia (where there is a high frequency of DR2), and D. C. G. Skegg and colleagues (1987) have shown that multiple sclerosis is three times less common in the north than in the south of New Zealand - the latter a site of preferential migration for the Scots, who have a particularly high frequency of DR2.

There are fewer data for non-Caucasoid populations. In a small study, multiple sclerosis was found to be associated with the Dw2 (related to DR2) in blacks in Philadelphia. Among the Arabs, multiple sclerosis is associated with DR2 in some groups, and DR4 in others. No HLA association has been found in the Japanese and Israelis.

It should be noted that multiple sclerosis is rare in two populations in which DR2 is common: the Hungarian Gypsies (of whom 56 percent of controls are DR2 positive) as well as the Maoris - raising the possibility of the existence of an overriding genetic protective effect. Protective genes have also been postulated in Mongoloid and Caucasoid populations. Moreover, current research suggests that multiple sclerosis may be associated with peculiarities in the structure of certain genes in the HLA region.

What is one to make of this mass of confusing and sometimes conflicting data? The frequency with which some association with the HLA system is found suggests that the observations are significant. Yet it is clear that none of the factors so far identified alone confer susceptibility to the disease. The simplest explanation would be that DR2 is acting as a marker for another gene (or genes) conferring susceptibility, and that other genetic factors are involved as well.

Other possible genetic associations have been little studied, although there is evidence for an association with genes concerned with the control of antibody structure located on the fourteenth chromosome. A consistent pattern has not yet emerged. What is common to all the genetic associations so far identified is that they are concerned in one way or another with the genetic control of the immune response.

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