Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study.
Excess of nitric oxide (NO) has been shown to exert neurotoxic impacts in the brain. Moreover, inhibition of two NO-synthesizing enzymes, neuronal NOS (nNOS) and inducible NOS (iNOS), displays neuroprotective effects in the MPTP model of Parkinson's disease (PD). These data suggest a possible involvement of NOS as factors controlling the resistance of the nigral dopaminergic neurons to environmental insults. Therefore, we investigated whether polymorphisms present in these genes could contribute to the risk of developing PD. We carried out a community-based case-control study among subjects enrolled in the Mutualité Sociale Agricole, the French health insurance organization for workers connected to agriculture. Two-hundred and nine PD patients and 488 controls of European (mostly French) ancestry and matched for age, sex and region of residency were included in this study. Associations were observed with polymorphisms present in exon 22 of iNOS (OR for AA carriers=0.50, 95% CI=0.29-0.86, P=0.01) and in exon 29 of nNOS (OR for carriers of the T allele=1.53, 95% CI=1.08-2.16, P=0.02); no association was observed with a polymorphism in exon 18 of nNOS (OR for carriers of the T allele=1.20, 95% CI=0.85-1.69, P=0.30). Moreover, a significant interaction of the nNOS polymorphisms with current and ever cigarette smoking was found (nNOS 18, P=0.05; nNOS 29, P=0.04). All together, these data favour an involvement of these two genes as new modifier genes in PD.
Levecque
Clotilde
C
INSERM Unit 508 Institut Pasteur de Lille, 59019 Lille, France.
Elbaz
Alexis
A
Clavel
Jacqueline
J
Richard
Florence
F
Vidal
Jean-Sébastien
JS
Amouyel
Philippe
P
Tzourio
Christophe
C
Alpérovitch
Annick
A
Chartier-Harlin
Marie-Christine
MC
D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology
D009566:Nitrates; D009569:Nitric Oxide; C496320:NOS1 protein, human; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II