Article

Lack of association of the COMT (Val 158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies.

Molecular Psychiatry 01/2005; 10:765-770. pp.765-770
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    Article: Psychiatric genetics: progress amid controversy.
    Margit Burmeister, Melvin G McInnis, Sebastian Zöllner
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    ABSTRACT: Several psychiatric disorders--such as bipolar disorder, schizophrenia and autism--are highly heritable, yet identifying their genetic basis has been challenging, with most discoveries failing to be replicated. However, inroads have been made by the incorporation of intermediate traits (endophenotypes) and of environmental factors into genetic analyses, and through the identification of rare inherited variants and novel structural mutations. Current efforts aim to increase sample sizes by gathering larger samples for case-control studies or through meta-analyses of such studies. More attention on unique families, rare variants, and on incorporating environment and the emerging knowledge of biological function and pathways into genetic analysis is warranted.
    Nature Reviews Genetics 08/2008; 9(7):527-40. · 38.08 Impact Factor
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    Article: HapMap tag-SNP analysis confirms a role for COMT in schizophrenia risk and reveals a novel association.
    J Voisey, C D Swagell, I P Hughes, B R Lawford, R M Young, C P Morris
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    ABSTRACT: Catechol-O-methyl transferase (COMT) encodes an enzyme involved in the metabolism of dopamine and maps to a commonly deleted region that increases schizophrenia risk. A non-synonymous polymorphism (rs4680) in COMT has been previously found to be associated with schizophrenia and results in altered activity levels of COMT. Using a haplotype block-based gene-tagging approach we conducted an association study of seven COMT single nucleotide polymorphisms (SNPs) in 160 patients with a DSM-IV diagnosis of schizophrenia and 250 controls in an Australian population. Two polymorphisms including rs4680 and rs165774 were found to be significantly associated with schizophrenia. The rs4680 results in a Val/Met substitution but the strongest association was shown by the novel SNP, rs165774, which may still be functional even though it is located in intron five. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. This association was slightly improved when males were analysed separately possibly indicating a degree of sexual dimorphism. Our results confirm that COMT is a good candidate for schizophrenia risk, by replicating the association with rs4680 and identifying a novel SNP association.
    European Psychiatry 10/2010; 27(5):372-6. · 2.77 Impact Factor
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    Article: No Association Between Functional Polymorphisms in COMT and MTHFR and Schizophrenia Risk in Korean Population.
    Ho Jin Kang, Byeong Moo Choe, Seong Hwan Kim, Seung-Rak Son, Kyoung-Mu Lee, Byoung Gwon Kim, Young-Seoub Hong
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    ABSTRACT: Common genetic SNPs in two genes, encoding catechol-O-methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR), which are interconnected with COMT gene regulation, have been reported to contribute to schizophrenia risk. In this study, we evaluated the association between functional polymorphisms in COMT and MTHFR and schizophrenia risk with a case-control study in a Korean population. We performed a case-control study by genotyping analysis using 360 cases and 348 controls in Korean subjects to determine the association between functional polymorphisms in COMT and MTHFR and schizophrenia risk. Four functional SNPs in COMT (Val158Met and rs165599) and MTHFR (C677T and A1298C) were genotyped by primer extension assay. None of the genotype distributions for the four SNPs was significantly different between cases and controls. Stratified analysis did not show any significant gender difference for any polymorphism. In addition, we found no evidence of a gene-gene interaction in the analysis of combined genotypes. Our results suggest no significant association between the selected functional polymorphisms of COMT or MTHFR in Korean schizophrenia subjects. However, further studies are required to confirm our findings in a larger number of subjects.
    Epidemiology and health. 01/2010; 32:e2010011.

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