Catechol-O-methyltransferase gene Val108/158Met polymorphism, and susceptibility to schizophrenia: association is more significant in women

• DOI: 10.1016/j.molbrainres.2004.09.005
• Publication Date: 2004-11-16T14:05:01Z
• Authors: Ali Sazci; Emel Ergul; Ismail Kucukali; Gamze Kilic; Guner Kaya; Ihsan Kara
• Keywords: Adult; Male; Polymorphism, Genetic; Genotype; Turkey; DNA Mutational Analysis; Valine; Middle Aged; Catechol O-Methyltransferase; 03 medical and health sciences; Methionine; Sex Factors; 0302 clinical medicine; Amino Acid Substitution; Gene Frequency; Risk Factors; Mutation; Schizophrenia; Humans; Female; Genetic Predisposition to Disease; Genetic Testing

Schizophrenia is a complex disorder with a polygenic inheritance. Catechol-O-methyltransferase (COMT) plays a significant role in the regulation of dopaminergic systems. A polymorphism at COMT Val108/158Met has been identified in association with schizophrenia. We examined the allele and genotype association of the COMT Val108/158Met polymorphism of 297 unrelated schizophrenic patients who strictly met DSM-IV criteria for schizophrenia, and 341 healthy controls. We found significant difference in allele and genotype frequencies between schizophrenic patients and controls (chi2=13.030; P=0.001). The allele frequency of the COMT-L was 45.79% in the total schizophrenic patients, and 41.50% in controls. The genotype frequency of the COM-LL was 21.2% in the total schizophrenic patients, and 11.4% in controls (OR=2.085; 95% CI=1.350-3.219; chi2=11.293; P=0.001). With a separate sex analysis, the frequency of the COMT-L allele was moderately distributed in male schizophrenia (chi2=6.177; df=2; P=0.046). The COMT-LL genotype had a 1.818-fold increased risk for schizophrenia (OR=1.818; 95% CI=1.010-3.273; chi2=4.048; P=0.044). The frequency of the COMT-L allele was even more significantly distributed in women schizophrenia (chi2=7.797; df=2; P=0.020). The COMT-LL genotype had remarkably more increased risk for schizophrenia (OR=2.456; 95% CI=1.287-4.687; chi2=7.710; P=0.005). In conclusion, our results provide strong evidence for a role of the COMT-L allele and LL genotype in the etiopathophysiology of schizophrenia with a sexual difference.