J Korean Med Sci.  2011 Oct;26(10):1356-1363. 10.3346/jkms.2011.26.10.1356.

No Association of Functional Polymorphisms in Methlylenetetrahydrofolate Reductase and the Risk and Minor Physical Anomalies of Schizophrenia in Korean Population

• Kim SG
• Song JY
• Joo EJ
• Jeong SH
• Kim SH
• Lee KY
• Lee NY
• Ahn YM
• Kim YS
• Roh MS

• KMID: 1785995
• DOI: http://doi.org/10.3346/jkms.2011.26.10.1356

Abstract

Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism, plays an important role in DNA methylation. It has been suggested that abnormal DNA methylation contributes to the pathogenesis of schizophrenia and congenital anomalies. The previous findings regarding the genetic relationship between MTHFR and schizophrenia are controversial. This study investigated the association of the two functional polymorphisms of MTHFR, C677T and A1298C, with the risk for schizophrenia. Furthermore, we conducted an updated meta-analysis on the two polymorphisms. In addition, we investigated the relationship between the polymorphisms and minor physical anomaly (MPA), which may represent neurodevelopmental aberrations in 201 schizophrenia patients and 350 normal control subjects. There was no significant association between either of the two polymorphisms and the risk of schizophrenia (chi-square = 0.001, df = 1, P = 0.971 for C677T; chi-square = 1.319, df = 1, P = 0.251 for A1298C). However, in meta-analysis, the C677T polymorphism showed a significant association in the combined and Asian populations (OR = 1.13, P = 0.005; OR = 1.21, P = 0.011, respectively) but not in the Korean and Caucasian populations alone. Neither polymorphism was associated with MPAs measured by the Waldrop scale (chi-square = 2.513, df = 2, P = 0.285). In conclusion, the present findings suggest that in the Korean population, the MTHFR polymorphisms are unlikely to be associated with the risk for schizophrenia and neurodevelopmental abnormalities related to schizophrenia.

Keyword

Case-Control Studies; Polymorphism, Genetic; Korean; Meta-Analysis; Methylenetetrahydrofolate Reductase; Schizophrenia

MeSH Terms

Adult
Alleles
Case-Control Studies
Congenital Abnormalities/*genetics
DNA Methylation
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
Male
Methylenetetrahydrofolate Reductase (NADPH2)/*genetics
Middle Aged
*Polymorphism, Single Nucleotide
Republic of Korea
Schizophrenia/*genetics/pathology

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