Absence of linkage with the neuronal nitric oxide synthase (NOS1) gene in 41 multiplex Swedish MS families

Several genetic factors are likely to play a role in the aetiology of multiple sclerosis (MS), although so far only the HLA gene complex has been clearly identified as important. In addition, several studies support the importance of nitric oxide synthase (NOS) as a component in the pathogenesis of MS. We have investigated the role of the neuronal nitric oxide synthase (NOS1) gene in 41 Swedish multiplex MS families by parametric and nonparametric linkage analysis with two polymorphic intragenic markers. Two-point lod scores were clearly negative, effectively excluding a role of the NOS1 gene in most models tested. Non-parametric linkage analysis (NPL), affected pedigree member (APM) analysis and extended transmission disequilibrium test (ETDT) also failed to provide evidence for a susceptibility locus in this gene. Thus, a contribution of the NOS1 gene to the genetic background of MS is unlikely in this population.