Novel Susceptibility Loci Identified in Multiple Sclerosis

At least 29 loci identified, including immunologically relevant genes influencing T-cell maturation

THURSDAY, Aug. 11 (HealthDay News) -- An international genome-wide association study has revealed at least 29 novel susceptibility loci involved in multiple sclerosis (MS), many of which are immunologically relevant, according to a letter published in the Aug. 11 issue of Nature.

Stephen Sawcer, M.B., Ch.B., Ph.D., from the University of Cambridge in the United Kingdom, and colleagues ascertained the genetic risk and role for cell-mediated immune mechanisms in MS. A genome-wide association study comprising 9,772 cases of European descent from 23 research groups in 15 countries through the International Multiple Sclerosis Genetics Consortium were compared with 17,376 controls from the Wellcome Trust Case Control Consortium 2 project. Data from 465,434 autosomal single nucleotide polymorphisms (SNPs) were analyzed, and enrichment of genes with similar function was objectively assessed.

The investigators identified 23 of the 26 previously known or strongly suggested MS-associated loci, and revealed at least 29 novel susceptibility loci. Pathway analysis implicated genes coding for cytokine pathway, co-stimulatory, and signal transduction molecules of immunological relevance. The functionally relevant genes with the most significant enrichment included genes linked to lymphocyte function, particularly those involved in T-cell activation and proliferation. Several of the genes involved in the T-helper-cell differentiation showed strong evidence of association with MS. Classical human leukocyte antigen (HLA) types at six loci and SNP alleles were analysed and HLA-DRB1 was found to have the strongest association with MS. The independent protective effect attributable to the class I region was confirmed to be due to variation in the HLA-A gene.

"Immunologically relevant genes are significantly over-represented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis," the authors write.

Abstract
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Physician’s Briefing Staff

Physician’s Briefing Staff

Published on August 11, 2011

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