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KMID : 0389420080160020085
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Korean Journal of Stress Research
2008 Volume.16 No. 2 p.85 ~ p.91
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Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms and Korean Patients with Schizophrenia
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Cho Ah-Rang
Kim Bum-Shik
Kim Yong-Ho
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Abstract
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High levels of homocysteine promote oxidative stress, and aberrant homocysteine metabolism is linked to neurodevelopmental disorders including schizophrenia. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. The present study was conducted to examine the association between the MTHFR gene and schizophrenia in Korean population. Subjects of 279 patients with schizophrenia and 296 healthy controls were recruited. We genotyped two single nucleotide polymorphisms (SNPs, rs2274976 and rs1801133) using the Illumina Sentrix Array Matrix chip and direct sequencing. The rs2274976 (Arg594Gln) is located on exon 12 of the MTHFR gene region, and the rs1801133 (Ala222Val) located on exon 5. For the analysis of genetic data, SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used. Multiple logistic regression analysis (codominant, dominant, and recessive models) was also used. Patients with schizophrenia were evaluated according to clinical manifestations using the Operational Criteria Checklist (OPCRIT). Two SNPs (rs2274976 and rs1801133) were not associated with schizophrenia. However, one SNP showed a significant association with one phenotype of psychotic symptoms. Running commanding voices, which could be clinically considered serious feature of auditory hallucinations, was different in the recessive model (p=0.018; p=0.036 after Bonferroni correction). Recently, rs59514310 replaces rs1801133 as new number (SNP database, BUILD 129). In present study, a significant association was observed between rs1801133 and running commanding voices. The result suggests that the MTHFR gene may be a susceptibility gene for schizophrenia with auditory hallucination.
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KEYWORD
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Auditory hallucination, Methylenetetrahydrofolate Reductase (MTHFR), Schizophrenia, Single nucleotide polymorphism
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