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Lack of association of catechol-O-methyltransferase gene Val108/158Met polymorphism with schizophrenia: a family-based association study in a Chinese population

Molecular Psychiatry volume 11, pages 2–3 (2006)Cite this article

SIR—Catechol-O-methyltransferase (COMT) gene has been considered to be one of the candidate genes for schizophrenia because it encodes one of the major enzymes for dopamine metabolism and also lies on chromosome band 22q11.2, which has long been associated with schizophrenia susceptibility.1 COMT has a common functional polymorphism, a single-nucleotide polymorphism at position 108/158 that results in a change from valine (Val) to methionine (Met); the Val variant has a higher enzymatic activity, leading to increased degradation of dopamine.2 The association of this COMT Val108/158Met polymorphism with schizophrenia has long been a focus of genetic studies into schizophrenia. However, the results of studies of this genetic variant in schizophrenic subjects are inconsistent. Recently, Munafo et al3 demonstrated that there was evidence of a significant association between the COMT Val allele and schizophrenia risk, when all case–control studies were included in a meta-regression. However, when only studies that reported allele frequencies in the controls that did not deviate significantly from Hardy–Weinberg equilibrium were included, these results were no longer significant. As case–control studies carry an increased risk of confounding by population stratification, the family-based designs could be a more reliable method to test the possible implication of the COMT Val108/158Met polymorphism in schizophrenia susceptibility. In a meta-analysis of family-based association studies, Glatt et al4 reported that the Val allele may be a small but reliable risk factor for schizophrenia in the Caucasian population, but the influence of this polymorphism on risk in Asian populations (from three studies; two with Chinese subjects and one with Japanese participants) remains unclear. In the study of a Chinese population, Li et al5 first reported an excess transmission of the Val allele among 178 family trios with schizophrenia. However, this finding was not reproduced in a subsequent study of 166 Chinese schizophrenia trios.6

To further clarify the role of COMT in schizophrenia in the Chinese population, we tested the transmission of the COMT Val108/158Met polymorphism in 220 trios consisting of Han Chinese schizophrenic subjects and their biological parents. All patients (91 female subjects and 129 male subjects; mean age 30.3 (SD±8.2) years) were psychiatric in-patients diagnosed from relevant criteria identified at interview and in medical records according to the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV). The diagnoses were re-evaluated by a senior psychiatrist. The method for genotyping the COMT Val108/158Met polymorphism is detailed in our previous report.7 The study was approved by the Institution Review Board of the Taipei Veterans General Hospital and informed consent was obtained from each participant in advance.

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Acknowledgements

This work was supported by Grant CH-91-16 from the Cheng-Hsin Rehabilitation and Medical Center, and Grant VGH-90-238 from the Taipei Veterans General Hospital.

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Authors and Affiliations

  1. Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

    S-J Tsai & C-J Hong

  2. Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    S-J Tsai & C-J Hong

  3. Division of Psychiatry, Cheng-Hsin Rehabilitation and Medical Center, Taipei, Taiwan

    S-J Hou & F-C Yen

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  1. S-J Tsai
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Correspondence to S-J Tsai.

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Tsai, SJ., Hong, CJ., Hou, SJ. et al. Lack of association of catechol-O-methyltransferase gene Val108/158Met polymorphism with schizophrenia: a family-based association study in a Chinese population. Mol Psychiatry 11, 2–3 (2006). https://doi.org/10.1038/sj.mp.4001736

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