Genetic association analysis of neuronal nitric oxide synthase gene polymorphism with tardive dyskinesia.
Possible involvement of oxidative stress in the pathophysiology of tardive dyskinesia (TD) has been proposed. Long-term administration of neuroleptics alters dopaminergic turnover, yielding the increase of the formation of reactive oxygen species (ROS), which may lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a polymorphism of the neuronal nitric oxide synthase (NOS1) gene whose reaction product, nitric oxide (NO), is involved in oxidative stress was studied in 171 Japanese patients with schizophrenia, including 41 patients meeting TD criteria. The C/T polymorphism in exon 29 of the NOS1 gene was genotyped using polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion. No significant difference in genotype frequencies was detected between subjects with and without TD (chi2 = 1.54, df = 2, p = 0.46). In addition, there was no difference in allele frequencies (chi2 = 0.42, df = 1, p = 0.51). These results suggest that the NOS1 gene polymorphism may not confer increased susceptibility to TD, although more investigations on other populations are warranted.
Shinkai
Takahiro
T
Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan. takahiro_shinkai@camh.net
Ohmori
Osamu
O
Matsumoto
Chima
C
Hori
Hiroko
H
Kennedy
James L
JL
Nakamura
Jun
J
D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects; D001921:Brain / Q000201:enzymology / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D004252:DNA Mutational Analysis; D004409:Dyskinesia, Drug-Induced / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics
D014150:Antipsychotic Agents; D009569:Nitric Oxide; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I