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NOS2A and the modulating effect of cigarette smoking in Parkinson's disease.

Publication ,  Journal Article
Hancock, DB; Martin, ER; Fujiwara, K; Stacy, MA; Scott, BL; Stajich, JM; Jewett, R; Li, Y-J; Hauser, MA; Vance, JM; Scott, WK
Published in: Ann Neurol
September 2006

OBJECTIVE: Inducible nitric oxide synthase, a protein product of NOS2A, generates nitric oxide as a defense mechanism, but excessive levels threaten cellular survival. NOS2A is a candidate gene for Parkinson's disease (PD) that potentially interacts with cigarette smoking. We examined NOS2A for association with PD risk and age at onset (AAO) and for interaction with smoking. METHODS: We genotyped 13 NOS2A single nucleotide polymorphisms (SNPs) in 466 singleton families and in a validation set of 286 multiplex families. We tested allelic and haplotypic association using the association in the presence of linkage test, genotypic associations using the genotype pedigree disequilibrium test, AAO effects using the quantitative transmission disequilibrium test, and interactions using generalized estimating equations. RESULTS: Among the pooled earliest onset families, rs2255929 and rs1060826 generated significant allelic (p = 0.000059 and 0.0062, respectively) and genotypic (p = 0.0039 and 0.0014, respectively) associations with risk and AAO (p = 0.00070 and 0.0073, respectively); the two-SNP haplotype generated even stronger association with PD (p = 0.000013). Significant interactions with smoking (p = 0.0015 for rs 2255929 and p < 0.0001 for rs 1060826) were detected in a subset of the families; smoking was inversely associated with PD among risk allele noncarriers, but significance diminished among carriers. INTERPRETATION: Our findings support NOS2A as a genetic risk factor in PD, potentially by influencing AAO and by modifying the inverse association between PD and smoking.

Duke Scholars

Published In

Ann Neurol

DOI

ISSN

0364-5134

Publication Date

September 2006

Volume

60

Issue

3

Start / End Page

366 / 373

Location

United States

Related Subject Headings

  • Smoking
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Parkinson Disease
  • Nitric Oxide Synthase Type II
  • Neurology & Neurosurgery
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Humans
 

Citation

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ICMJE
MLA
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Hancock, D. B., Martin, E. R., Fujiwara, K., Stacy, M. A., Scott, B. L., Stajich, J. M., … Scott, W. K. (2006). NOS2A and the modulating effect of cigarette smoking in Parkinson's disease. Ann Neurol, 60(3), 366–373. https://doi.org/10.1002/ana.20915
Hancock, Dana B., Eden R. Martin, Kenichiro Fujiwara, Mark A. Stacy, Burton L. Scott, Jeffrey M. Stajich, Rita Jewett, et al. “NOS2A and the modulating effect of cigarette smoking in Parkinson's disease.Ann Neurol 60, no. 3 (September 2006): 366–73. https://doi.org/10.1002/ana.20915.
Hancock DB, Martin ER, Fujiwara K, Stacy MA, Scott BL, Stajich JM, et al. NOS2A and the modulating effect of cigarette smoking in Parkinson's disease. Ann Neurol. 2006 Sep;60(3):366–73.
Hancock, Dana B., et al. “NOS2A and the modulating effect of cigarette smoking in Parkinson's disease.Ann Neurol, vol. 60, no. 3, Sept. 2006, pp. 366–73. Pubmed, doi:10.1002/ana.20915.
Hancock DB, Martin ER, Fujiwara K, Stacy MA, Scott BL, Stajich JM, Jewett R, Li Y-J, Hauser MA, Vance JM, Scott WK. NOS2A and the modulating effect of cigarette smoking in Parkinson's disease. Ann Neurol. 2006 Sep;60(3):366–373.
Journal cover image

Published In

Ann Neurol

DOI

ISSN

0364-5134

Publication Date

September 2006

Volume

60

Issue

3

Start / End Page

366 / 373

Location

United States

Related Subject Headings

  • Smoking
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Parkinson Disease
  • Nitric Oxide Synthase Type II
  • Neurology & Neurosurgery
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Humans