TNFRSF1A polymorphisms and MS: Statistical signals transform into pathogenetic mechanisms.

摘要

A genetic contribution to multiple sclerosis (MS) risk is now well-established, the strongest contributor being human leukocyte antigen (HLA). The quest for non-HLA MS susceptibility genes has reached a new level during the past 5 years through the application of genome-wide association studies. International consortia have designed studies with adequate power to identify susceptibility loci with substantially weaker effects than HLA. More than 50 such loci were recently confirmed or suggested in a large international analysis of 9,772 patients with MS and 17,376 controls.(1) A strikingly high proportion of the identified loci code for immune system components, in particular cytokine pathways, costimulation, and signal transduction, many of these linked with T-cell activation and T-helper-cell differentiation.