NOS2A and the modulating effect of cigarette smoking in Parkinson's disease
Identifieur interne : 001255 ( Main/Exploration ); précédent : 001254; suivant : 001256NOS2A and the modulating effect of cigarette smoking in Parkinson's disease
Auteurs : Dana B. Hancock [États-Unis] ; Eden R. Martin [États-Unis] ; Kenichiro Fujiwara [États-Unis] ; Mark A. Stacy [États-Unis] ; Burton L. Scott [États-Unis] ; Jeffrey M. Stajich [États-Unis] ; Rita Jewett [États-Unis] ; Yi-Ju Li [États-Unis] ; Michael A. Hauser [États-Unis] ; Jeffery M. Vance [États-Unis] ; William K. Scott [États-Unis]Source :
- Annals of Neurology [ 0364-5134 ] ; 2006-09.
Abstract
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. Ann Neurol 2006
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DOI: 10.1002/ana.20915
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Vance</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Center for Human Genetics, Duke University Medical Center, Durham</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Medicine, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William K." last="Scott">William K. 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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. Ann Neurol 2006</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li></region></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Hancock, Dana B" sort="Hancock, Dana B" uniqKey="Hancock D" first="Dana B." last="Hancock">Dana B. Hancock</name></region><name sortKey="Fujiwara, Kenichiro" sort="Fujiwara, Kenichiro" uniqKey="Fujiwara K" first="Kenichiro" last="Fujiwara">Kenichiro Fujiwara</name><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A." last="Hauser">Michael A. Hauser</name><name sortKey="Hauser, Michael A" sort="Hauser, Michael A" uniqKey="Hauser M" first="Michael A." last="Hauser">Michael A. Hauser</name><name sortKey="Jewett, Rita" sort="Jewett, Rita" uniqKey="Jewett R" first="Rita" last="Jewett">Rita Jewett</name><name sortKey="Li, Yi U" sort="Li, Yi U" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name><name sortKey="Li, Yi U" sort="Li, Yi U" uniqKey="Li Y" first="Yi-Ju" last="Li">Yi-Ju Li</name><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden R." last="Martin">Eden R. Martin</name><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden R." last="Martin">Eden R. Martin</name><name sortKey="Scott, Burton L" sort="Scott, Burton L" uniqKey="Scott B" first="Burton L." last="Scott">Burton L. Scott</name><name sortKey="Scott, Burton L" sort="Scott, Burton L" uniqKey="Scott B" first="Burton L." last="Scott">Burton L. Scott</name><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William K." last="Scott">William K. Scott</name><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William K." last="Scott">William K. Scott</name><name sortKey="Stacy, Mark A" sort="Stacy, Mark A" uniqKey="Stacy M" first="Mark A." last="Stacy">Mark A. Stacy</name><name sortKey="Stacy, Mark A" sort="Stacy, Mark A" uniqKey="Stacy M" first="Mark A." last="Stacy">Mark A. Stacy</name><name sortKey="Stajich, Jeffrey M" sort="Stajich, Jeffrey M" uniqKey="Stajich J" first="Jeffrey M." last="Stajich">Jeffrey M. Stajich</name><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery M." last="Vance">Jeffery M. Vance</name><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery M." last="Vance">Jeffery M. Vance</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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