한국인 정신분열병환자에서 MTHFR 유전자의 단일 염기다형성인 C677T와 A1298C의 연관성 분석
Association Analysis of MTHFR C677T, A1298C Gene Polymorphism in Korean Schizophrenic Patients
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Objectives：Methylenetetrahydrofolate reductase(MTHFR) plays an important role in folate metabolism, and the C677T and A1298C single nucleotide polymorphisms(SNPs) of the MTHFR gene may be associated with schizophrenia. The relationship between MTHFR SNPs and schizophrenia is unclear in Korean schizophrenic patients. The purpose in this study was to determine the association between the MTHFR gene SNPs and schizophrenia in Korean patients. Methods：Three hundred and sixty six patients with schizophrenia and 359 normal control subjects were used to identify the SNPs. Genetic analysis was carried out in the C677T and A1298C SNP regions using the SNP-ITTM assay. The allele, genotype and haplotype frequencies were compared between the two groups. The subgroups were divided on the basis of the onset age, and the allele frequencies and genotype frequencies were individually compared among the subgroups. Results：Gene variation of the MTHFR C677T and A1298C SNPs did not show significant differences between the schizophrenic patients and controls. In addition, no association between their SNPs and the onset age of schizophrenia was found. Conclusion：A genetic association between the C677T and A1298C SNPs on the MTHFR gene and Korean schizophrenic patients was not found in this study.
Abstract
Objectives：Methylenetetrahydrofolate reductase(MTHFR) plays an important role in folate metabolism, and the C677T and A1298C single nucleotide polymorphisms(SNPs) of the MTHFR gene may be associated with schizophrenia. The relationship between MTHFR SNPs and schizophrenia is unclear in Korean schizophrenic patients. The purpose in this study was to determine the association between the MTHFR gene SNPs and schizophrenia in Korean patients. Methods：Three hundred and sixty six patients with schizophrenia and 359 normal control subjects were used to identify the SNPs. Genetic analysis was carried out in the C677T and A1298C SNP regions using the SNP-ITTM assay. The allele, genotype and haplotype frequencies were compared between the two groups. The subgroups were divided on the basis of the onset age, and the allele frequencies and genotype frequencies were individually compared among the subgroups. Results：Gene variation of the MTHFR C677T and A1298C SNPs did not show significant differences between the schizophrenic patients and controls. In addition, no association between their SNPs and the onset age of schizophrenia was found. Conclusion：A genetic association between the C677T and A1298C SNPs on the MTHFR gene and Korean schizophrenic patients was not found in this study.
참고문헌 (23)
- Alpert JE, "Nutrition and depression: focus on folate", Nutrition, 16, pp.544~546 (2000)
- Goff DC, "Folate, homocysteine, and negative symptoms in schizophrenia", Am J Psychiatry, 161, pp.1705~1708 (2004)
- Levine J, "Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia", Biol Psychiatry, 60, pp.265~269 (2006)
- Elliott GR, "N5,10-methylenetetrahydrofolate reductase activity in autopsied brain parts of chronic schizophrenics and controls and in vitro tryptoline formation", Biol Psychiatry, 13, pp.695~708 (1978)
- van der Put NM, "A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?", Am J Hum Genet, 62, pp.1044~1051 (1998)
- Freeman JM, "Folate-responsive homocystinuria and "schizophrenia". A defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity", N Engl J Med, 292, pp.491~496 (1975)
- Bjornsson HT, "An integrated epigenetic and genetic approach to common human disease", Trends Genet, 20, pp.350~358 (2004)
- Goyette P, "Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification", Nat Genet, 7, pp.195~200 (1994)
- Rozen R, "Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetra -hydrofolate reductase(MTHFR)", Thromb Haemost, 78, pp.523~526 (1997)
- Frosst P, "A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase", Nat Genet, 10, pp.111~113 (1995)
- Muntjewerff JW, "Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: a Dutch population based case-control study", Am J Med Genet B Neuropsychiatr Genet, 135, pp.69~72 (2005)
- Sazci A, "Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene with schizophrenia: association is significant in men but not in women", Prog Neuropsychopharmacol Biol Psychiatry, 29, pp.1113~1123 (2005)
- Virgos C, "Plasma homocysteine and the methylenetetrahydrofolate reductase C677T gene variant: lack of association with schizophrenia", Neuroreport, 10, pp.2035~2038 (1999)
- Kunugi H, "C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses", Mol Psychiatry, 3, pp.435~437 (1998)
- Zintzaras E, "C677T and A1298C methylenetetrahydrofolate reductase gene polymorphisms in schizophrenia, bipolar disorder and depression: a meta-analysis of genetic association studies", Psychiatr Genet, 16, pp.105~115 (2006)
- Weisberg I, "A second genetic polymorphism in methylenetetrahydrofolate reductase(MTHFR) associated with decreased enzyme activity", Mol Genet Metab, 64, pp.169~172 (1998)
- Vilella E, "Further evidence that hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T and A1289C polymorphisms are not risk factors for schizophrenia", Prog Neuropsychopharmacol Biol Psychiatry, 29, pp.1169~1174 (2005)
- Lee YS, "Serum homocysteine, folate level and methylenetetrahydrofolate reductase 677, 1298 gene polymorphism in Korean schizophrenic patients", Neuroreport, 17, pp.743~746 (2006)
- American Psychiatric Association, "Diagnostic and Statistical Manual of Mental Disorders" (1994), American Psychiatric Association
- Gudnason V, "C677T(thermolabile alanine", valine) polymorphism in methylenetetrahydrofolate reductase (MTHFR): its frequency and impact on plasma homocysteine concentration in different European populations. EARS group, 1998, pp.136, 347~354
- Arinami T, "Methylenetetrahydrofolate reductase variant and schizophrenia", depression, 1997, pp.74, 526~528
- Levine J, "Elevated homocysteine levels in young male patients with schizophrenia", Am J Psychiatry, 159, pp.1790~1792 (2002)
- Regland B, "Homozygous thermolabile methylenetetrahydrofolate reductase in schizophrenia-like psychosis", J Neural Transm, 104, pp.931~941 (1997)