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

L. F. Barcellos, P. P. Ramsay, S. J. Caillier, S. Sawcer, J. Haines, S. Schmidt, M. Pericak-Vance, D. A.S. Compston, P. Gabatto, S. L. Hauser, J. R. Oksenberg

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalGenes and Immunity
Volume9
Issue number6
DOIs
StatePublished - Jun 27 2008

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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    Barcellos, L. F., Ramsay, P. P., Caillier, S. J., Sawcer, S., Haines, J., Schmidt, S., Pericak-Vance, M., Compston, D. A. S., Gabatto, P., Hauser, S. L., & Oksenberg, J. R. (2008). Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis. Genes and Immunity, 9(6), 493-500. https://doi.org/10.1038/gene.2008.41