The influence of non-HLA gene polymorphisms and interactions on disease risk in a Western Australian multiple sclerosis cohort

Non-Human Leukocyte Antigen (HLA) genes have concomitant, although modest, effects on multiple sclerosis (MS) susceptibility; however findings have varied in different populations. Here we present the results of an association study of 16 single nucleotide polymorphisms (SNPs) in 10 non-HLA genes (IL7R, IL2RA, CLEC-16A, TYK2, CD58, IRF5, STAT3, CTLA-4, APOE, ICAM-1) in a Western Australian cohort of 350 MS patients and 498 population control subjects. Our results indicate that in this population, SNPs in IL7R, TYK2, IRF5 and APOE have modifying effects on MS susceptibility. We also found evidence of interactive protective effects between polymorphisms in the IL7R/CD58, CLEC-16A/CTLA-4, and TYK2/IRF5 genes, which in some instances are restricted within HLA- or gender-defined groups.