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- Title
Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis.
- Authors
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.
- 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.Genes and Immunity (2008) 9, 493–500; doi:10.1038/gene.2008.41; published online 26 June 2008
- Subjects
NITRIC oxide; HUMAN genetic variation; MULTIPLE sclerosis risk factors; NERVOUS system abnormalities; GENETIC polymorphisms; GENES; IMMUNITY; GENETICS
- Publication
Genes & Immunity, 2008, Vol 9, Issue 6, p493
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/gene.2008.41