Human Molecular Genetics, 2003, Vol. 12, No. 1 79-86
© 2003 Oxford University Press
Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case–control study
1INSERM Unit 508 Institut Pasteur de Lille, Lille, France, 2INSERM Unit 360 Hôpital de la Salpêtrière, Paris, France, 3INSERM Unit 170, Villejuif, France and 4Service de Neurologie, Hôpital Saint-Antoine, Paris, France
Received September 16, 2002; Accepted November 11, 2002
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.
* To whom correspondence should be addressed at: INSERM Unit 508 Institut Pasteur de Lille, 1 rue du Pr Calmette, BP 245, 59019 Lille, France. Tel: +33 320877228; Fax: +33 320877894; Email: marie-christine.chartier{at}pasteur-lille.fr
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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