Genetic association analysis of functional polymorphisms in neuronal nitric oxide synthase 1 gene (NOS1) and mood disorders and fluvoxamine response in major depressive disorder in the Japanese population.
OBJECTIVE
Nitric oxide has been reported to play a role in neural transmitter release and N-methyl-D-aspartate receptor activation, as well as to be related to oxidative stress. Abnormalities in both of these mechanisms are thought to be involved in the pathophysiology of mood disorders including major depressive disorder (MDD) and bipolar disorder (BP). In addition, several lines of evidence support an association between abnormalities in neuronal nitric oxide synthases (nNOS) and mood disorders. Therefore, we studied the association of nNOS gene (NOS1) and mood disorders and the efficacy of fluvoxamine treatment in Japanese MDD patients.


METHODS
Using a single nucleotide polymorphism (SNP; rs41279104, also called ex1c), we conducted a genetic association analysis of case-control samples (325 MDD patients, 154 BP patients and 807 controls) in the Japanese population. In addition, we performed an association analysis between NOS1 and the efficacy of fluvoxamine treatment in 117 MDD patients. We defined a clinical response as a decrease of more than 50% in baseline SIGH-D (Structured Interview Guide for the Hamilton Rating Scale for Depression) score within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks.


RESULTS
We did not detect a significant association between NOS1 and MDD, BP or the fluvoxamine therapeutic response in MDD in allele/genotype-wise analysis.


CONCLUSIONS
We did not detect an association between only one marker (rs41279104) in NOS1 and Japanese mood disorder patients and fluvoxamine response, but sample sizes were probably too small to allow a meaningful test. Moreover, because we did not perform an association analysis based on linkage disequilibrium and a mutation scan of NOS1, a replication of the study using a larger sample and based on linkage disequilibrium may be required for conclusive results.
Okumura
Takenori
T
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.
Kishi
Taro
T
Okochi
Tomo
T
Ikeda
Masashi
M
Kitajima
Tsuyoshi
T
Yamanouchi
Yoshio
Y
Kinoshita
Yoko
Y
Kawashima
Kunihiro
K
Tsunoka
Tomoko
T
Inada
Toshiya
T
Ozaki
Norio
N
Iwata
Nakao
N
D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D016666:Fluvoxamine / Q000627:therapeutic use*; D005787:Gene Frequency; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D007564:Japan / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D018687:Antidepressive Agents, Second-Generation; D052248:Nitric Oxide Synthase Type I; D016666:Fluvoxamine