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

Genes & Immunity volume 9, pages 493–500 (2008)Cite this article

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.

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Acknowledgements

We are grateful to the MS patients and their family members for participating in this study. This work was funded by grants from the National Institute of Health (R01NS049510, R01NS26799 and NS032830), National Multiple Sclerosis Society (2901C6), the Nancy Davis Foundation, the Medical Research Council (G0000648) and the Wellcome Trust (057097). We thank the International Multiple Sclerosis Genetics Consortium for providing NOS2A SNP genotypes for 930 MS trio families to include in our analyses.

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Authors and Affiliations

  1. Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA

    L F Barcellos & P P Ramsay

  2. Department of Neurology, University of California, San Francisco, CA, USA

    L F Barcellos, S J Caillier, P Gabatto, S L Hauser & J R Oksenberg

  3. Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

    S Sawcer & D A S Compston

  4. Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA

    J Haines

  5. Center for Human Genetics, Duke University Medical Center, Durham, NC, USA

    S Schmidt

  6. Miami Institute for Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA

    M Pericak-Vance

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  1. L F Barcellos
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Correspondence to L F Barcellos.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Barcellos, L., Ramsay, P., Caillier, S. et al. Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis. Genes Immun 9, 493–500 (2008). https://doi.org/10.1038/gene.2008.41

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