Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis.
BACKGROUND
A common functional polymorphism (Val/Met) in the catechol-O-methyltransferase gene (COMT) that markedly affects enzyme activity has been shown to affect executive cognition and the physiology of the prefrontal cortex in humans. It is hypothesized that the high activity Val allele slightly increases risk for schizophrenia through its effect on dopamine-mediated prefrontal information processing.


METHODS
We compared the allele/genotype frequencies of the Val/Met polymorphism in a large independent patient-control sample (862 patient and 928 healthy control subjects) from Han Chinese population, and an update meta-analysis was performed to assess the collective evidence across individual studies.


RESULTS
No statistically significant differences were found in allele or genotype frequencies between patient and normal control subjects, although a nonsignificant overrepresentation of the Val allele in schizophrenia patients (odds ratio [OR] = 1.09, 95% confidence interval [CI] = .94-1.26) was suggested. Comparatively, the meta-analysis of all published population-based association studies showed statistically significant evidence for heterogeneity among the group of studies. Stratification of the studies by ethnicity of the samples yielded no significant evidence for an association with the Val allele in Asian population (OR = .96, 95% CI = .85-1.09), nor in European population (OR = 1.06, 95% CI = .95-1.19).


CONCLUSIONS
Our data provide minimal evidence that the Val allele is a susceptibility factor for schizophrenia in either European or Asian populations.
Fan
Jin-Bo
JB
Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences; Bio-X Life Science Research Center, Shanghai Jiao Tong University, China.
Zhang
Chang-Shun
CS
Gu
Niu-Fan
NF
Li
Xing-Wang
XW
Sun
Wei-Wei
WW
Wang
Hong-Yan
HY
Feng
Guo-Yin
GY
St Clair
David
D
He
Lin
L
D019943:Amino Acid Substitution; D044466:Asian People; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008297:Male; D008715:Methionine; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D014633:Valine
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine