Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: A large-scale association study plus meta-analysis

• Published in: Biological psychiatry (1969) Vol. 57; no. 2; pp. 139 - 144
• Main Authors: Fan, Jin-Bo, Zhang, Chang-Shun, Gu, Niu-Fan, Li, Xing-Wang, Sun, Wei-Wei, Wang, Hong-Yan, Feng, Guo-Yin, St. Clair, David, He, Lin
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.01.2005; Elsevier Science
• Subjects: Adult and adolescent clinical studies; Amino Acid Substitution; Asian Continental Ancestry Group; Association; Biological and medical sciences; Case-Control Studies; Catechol O-Methyltransferase - genetics; catechol-O-methyltransferase; China - epidemiology; Female; Gene Frequency - genetics; Genetic Predisposition to Disease; Genetics, Population; Humans; Male; Medical sciences; meta-analysis; Methionine; Polymorphism, Single Nucleotide - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - enzymology; Schizophrenia - ethnology; Schizophrenia - genetics; Valine; China; catechol-O-methyltransferase; meta-analysis; Association; schizophrenia; Human; Healthy subject; Enzyme; Transferases; Schizophrenia; Catechol O-methyltransferase; Ethnic group; Metaanalysis; Psychosis; Methyltransferases; Risk factor; Chinese; Comparative study; Polymorphism
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2004.10.018

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. 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. 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). Our data provide minimal evidence that the Val allele is a susceptibility factor for schizophrenia in either European or Asian populations.