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Genes Immun. 2008 Sep;9(6):493-500. doi: 10.1038/gene.2008.41. Epub 2008 Jun 26.

Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis.

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1
Division of Epidemiology, School of Public Health, University of California, Berkeley, CA 94720-7356, USA. barcello@genepi.berkeley.edu

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system with a strong genetic component. Variation in the major histocompatibility complex 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 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 6265 members from 1858 well-characterized MS families were utilized. No evidence for overtransmission of any individual single-nucleotide polymorphism 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.

PMID:
18580885
PMCID:
PMC4020442
DOI:
10.1038/gene.2008.41
[Indexed for MEDLINE]
Free PMC Article
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