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, Margaret A Pericak-Vance, D. A S Compston, P. Gabatto, S. L. Hauser, J. R. Oksenberg

Research output: Contribution to journalArticle

5 Citations (Scopus)

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

Fingerprint

Nitric Oxide Synthase
Multiple Sclerosis
Haplotypes
Chromosomes
Genes
HLA-DRB1 Chains
Central Nervous System Diseases
Major Histocompatibility Complex
Single Nucleotide Polymorphism
Disease Progression
Alleles

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Barcellos, L. F., Ramsay, P. P., Caillier, S. J., Sawcer, S., Haines, J., Schmidt, S., ... 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

Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis. / Barcellos, L. F.; Ramsay, P. P.; Caillier, S. J.; Sawcer, S.; Haines, J.; Schmidt, S.; Pericak-Vance, Margaret A; Compston, D. A S; Gabatto, P.; Hauser, S. L.; Oksenberg, J. R.

In: Genes and Immunity, Vol. 9, No. 6, 27.06.2008, p. 493-500.

Research output: Contribution to journalArticle

Barcellos, LF, Ramsay, PP, Caillier, SJ, Sawcer, S, Haines, J, Schmidt, S, Pericak-Vance, MA, Compston, DAS, Gabatto, P, Hauser, SL & Oksenberg, JR 2008, 'Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis', Genes and Immunity, vol. 9, no. 6, pp. 493-500. https://doi.org/10.1038/gene.2008.41
Barcellos LF, Ramsay PP, Caillier SJ, Sawcer S, Haines J, Schmidt S et al. Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis. Genes and Immunity. 2008 Jun 27;9(6):493-500. https://doi.org/10.1038/gene.2008.41
Barcellos, L. F. ; Ramsay, P. P. ; Caillier, S. J. ; Sawcer, S. ; Haines, J. ; Schmidt, S. ; Pericak-Vance, Margaret A ; Compston, D. A S ; Gabatto, P. ; Hauser, S. L. ; Oksenberg, J. R. / Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis. In: Genes and Immunity. 2008 ; Vol. 9, No. 6. pp. 493-500.
@article{01c5ae5443be49d3be45c1df598cb815,
title = "Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis",
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.",
author = "Barcellos, {L. F.} and Ramsay, {P. P.} and Caillier, {S. J.} and S. Sawcer and J. Haines and S. Schmidt and Pericak-Vance, {Margaret A} and Compston, {D. A S} and P. Gabatto and Hauser, {S. L.} and Oksenberg, {J. R.}",
year = "2008",
month = "6",
day = "27",
doi = "10.1038/gene.2008.41",
language = "English",
volume = "9",
pages = "493--500",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Genetic variation in nitric oxide synthase 2A (NOS2A) and risk for multiple sclerosis

AU - Barcellos, L. F.

AU - Ramsay, P. P.

AU - Caillier, S. J.

AU - Sawcer, S.

AU - Haines, J.

AU - Schmidt, S.

AU - Pericak-Vance, Margaret A

AU - Compston, D. A S

AU - Gabatto, P.

AU - Hauser, S. L.

AU - Oksenberg, J. R.

PY - 2008/6/27

Y1 - 2008/6/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=51249106669&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=51249106669&partnerID=8YFLogxK

U2 - 10.1038/gene.2008.41

DO - 10.1038/gene.2008.41

M3 - Article

C2 - 18580885

AN - SCOPUS:51249106669

VL - 9

SP - 493

EP - 500

JO - Genes and Immunity

JF - Genes and Immunity

SN - 1466-4879

IS - 6

ER -