The genetics of multiple sclerosis and its experimental models

Abstract

Purpose of review: We review the current thinking on the genetic aetiology of multiple sclerosis, new aspects of the influence of genes within the human leucocyte antigen (HLA) complex, how discrete non-HLA genes regulating multiple sclerosis start to be unequivocally demonstrated, and how knowledge from the genetics of experimental models of multiple sclerosis can be used.

Recent findings: Different alleles of the class II molecules display a hierarchy of risks including protective effects in multiple sclerosis. In addition, HLA class I genes are associated with the disease. Experimental multiple sclerosis models are regulated by many genes with small effects, more than about 100. Studies in humans suggest a similar situation. Indeed, the two genes unequivocally established, IL2RA and IL7RA, display a low odds ratio in the order of 1.3. We envisage that many more genes of this kind may be unravelled in the years to come.

Summary: There are hierarchies of influences from class II genes. Class I genes regulate disease as well. The unambiguous demonstration of non-HLA genes also suggests that many other genes impacting multiple sclerosis can be deciphered in the years to come. A complete knowledge of the most important of these may pave the way for more selective therapy and gene-environment studies.