Association study of catechol-O-methyltransferase gene polymorphisms with schizophrenia and psychopathological symptoms in Han Chinese

Abstract

Although dysfunction of catechol-O-methyltransferase (COMT)-mediated dopamine transmission is implicatedin the etiology of schizophrenia, the human COMT gene has not been associated consistently with schizophrenia. The purpose of this study was to investigate whether the COMT gene is associated with the development of schizophrenia and whether the polymorphisms of this gene influence the psychopathological symptoms in patients with schizophrenia. Fourteen polymorphisms of the COMT gene were analyzed in a case-control study of 876 Han Chinese individuals (434 patients and 442 controls). All participants were screened using a Chinese version of the modified Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) and all patients met the criteria for schizophrenia. Furthermore, pretreatment of psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) in a subset of 224 hospitalized schizophrenia patients, who were drugnaïve or drug-free, to examine the association between clinical symptomatology and COMT polymorphisms. No significant differences in allele or genotype frequencies were observed between schizophrenia patients and controls, for all variants investigated. Haplotype analysis showed that three haplotype blocks of the COMT gene were not associated with the development of schizophrenia. Moreover, these COMT polymorphisms did not influence the PANSS scores of schizophrenia patients. This study suggests that the COMT gene may not contribute to the risk of schizophrenia and to the psychopathological symptoms of schizophrenia among Han Chinese.

Generation and Characterization of Humanized Mice Carrying COMT158 Met/Val Alleles

“…A large number of human genetic association studies have been conducted to assess the association of COMT Val158Met with the risk of developing schizophrenia and other psychiatric disorders (Witte and Floel, 2012). Small increases in Val allele frequency have been reported in schizophrenia in some studies (Fan et al, 2005;Glatt et al, 2003), but in not others (Chen et al, 2011a;Nieratschker et al, 2010;Williams et al, 2005), while Met alleles are more frequent in some posttraumatic stress disorder (PTSD) populations (Boscarino et al, 2011;Kolassa et al, 2010;Valente et al, 2011). It is suggested that COMT predominantly affects dopamine metabolism in prefrontal cortex, where dopamine transporter expression is relatively low.…”

No Association of Catechol-O-Methyltransferase Polymorphisms with Schizophrenia in the Han Chinese Population

“…Meta-analyses do not support the association with SZ (Fan et al, 2005;Munafo et al, 2005;Okochi et al, 2009). Several previous studies in the Han Chinese population failed to find a positive association with SZ (Fan et al, 2005;Yu et al, 2007;Kang et al, 2010;Chen et al, 2011); but these studies chiefly focused on only one SNP and the sample sizes involved were relatively small.…”

Association of BDNF gene polymorphisms with schizophrenia and clinical symptoms in a Chinese population

“…First, population stratification could lead to a resetting of population gene frequencies. The sample from Taiwan may not be representative of the entire Han Chinese population, because of a possible population stratification bias [Yeh et al, ; Chen et al, ]. Second, the BDNF genotypes can be regarded as trait‐dependent features, while the assessment of illness intensity by PANSS is state‐dependent.…”