Two HLA class I genes independently associated with multiple sclerosis

Abstract

Objective: The risk of multiple sclerosis (MS) is influenced by HLA-DRB1, while protective effects have been proposed for HLA-A*02 and HLA-C*05. Our aim was to further understand the role of HLA class I in MS through a comprehensive investigation.

Methods: 1529 MS patients and 1814 controls from Sweden and Norway were genotyped for HLA-DRB1, HLA-A, and HLA-C. Simultaneous analysis of all alleles while adjusting for confounding was achieved using logistic regression.

Results: We observed independent effects of all three genes. We confirm the HLA-A*02 (OR=0.73, p=9.2 x 10(-4)) association and report a novel effect of HLA-C*08 (OR=1.85, p=0.0093).

Conclusions: The HLA class I region contains two factors modulating MS risk, characterized by independent associations with HLA-A and HLA-C.