HLA-class i markers and multiple sclerosis susceptibility in the Italian population

Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A02, HLA-Cw05 and MOG-142L. In this work, we tested the association with MS of A02 and Cw05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A02 conferred a statistically robust MS protection (odds ratio, OR0.61; 95% confidence intervals, CI0.51-0.72, P10 9), which was independent of DRB115 and of any other DRB1 allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for MOG-142L was secondary to its linkage disequilibrium with A02. Cw05 was not associated considering the whole sample, but its presence significantly enhanced the protection in the HLA-A02-positive group, independently of DRB1: the OR conferred by A02 in Cw05-positive individuals (0.22, 95% CI0.13-0.38) was significantly lower than in Cw05-negative individuals (0.69, 95% CI0.58-0.83) with a significant (P4.94 × 10 5) multiplicative interaction between the two markers. In the absence of A02, Cw05 behaved as a risk factor, particularly in combination with DRB103 (OR3.89, P0.0006), indicating that Cw05 might be a marker of protective or risk haplotypes, respectively.