Abstract
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) with a strong genetic component. Variation in the major histocompatibility complex (MHC) on chromosome 6p21, specifically the
HLA-DRB1*15
haplotype, is the strongest genetic factor for MS, yet it is estimated to account for only a portion of risk for the disease. Previous evidence has implicated the nitric oxide synthase gene (
NOS2A
) encoding inducible NOS (inos) on chromosome 17q11 as a potential MS susceptibility gene. To determine whether variation in the
NOS2A
gene contributes to MS risk, we investigated a total of 50 polymorphisms within or flanking the locus for evidence of association using a comprehensive analytical strategy. A total of 6,265 members from 1,858 well-characterized MS families were utilized. No evidence for over-transmission of any individual SNP allele or haplotype to the MS affected individuals was observed. Furthermore, different transmission rates were not observed in either
DRB1*15
positive or
DRB1*15
negative family subgroups, or when extreme clinical outcomes characterizing disease progression were examined. The very largest study of
NOS2A
variation in MS, to date, excludes even a modest role for this locus in susceptibility.
