Genes and susceptibility to multiple sclerosis

The balance of evidence relating to the aetiology of multiple sclerosis favours an interplay between genetic susceptibility and an environmental trigger. Just as the twin studies show clearly that almost 60% of monozygotic pairs are not concordant for multiple sclerosis (1-3), so also the low concordance rate in dizygotic twins, the rarity of conjugal multiple sclerosis (4), the lack of a birth order effect (9, and the identification of resistant groups living in high prevalence zones, all argue against a purely transmissible factor (6). A simple view would be that, of the candidate genes which have been examined as markers of susceptibility, only the DR15 class 2 major histocompatibility complex (MHC) allele association in northern Europeans holds up to critical analysis. The specifically different associations with DR4 in Japanese (7) and Jordanians (8) have never been confirmed although multiple sclerosis does appear to be DR4 associated in Sardinians (9). There is no evidence that any genetic marker, acting alone or in combination, protects individuals from development of the disease. Reports that the severity of multiple sclerosis correlates with the presence of specific susceptibility alleles, or that the primary progressive form of the disease is associated with a specifically different set of susceptibility markers (1 0), remain unconfirmed.