A Association Study Between Methylenetetrahydrofolate Reductase And Schizophrenia

Schizophrenia(SZ,MIM 181500) is a severe mental disorder characterized of abnormal thought, affection, behavior and the incongruity between environment and mental activity. Worldwide, the life-time prevalence of schizophrenia is 3.8-8.4‰. The forth leading cause of disability worldwide is SZ and it accounts for 2.6﹪ of diseases burden for the people aged from 15 to 44. Genetic factor is considered as the first factor because the heritability of SZ is greater than 80﹪. Compared with normal people, the risk of SZ is five-fold to tenfold in the first-degree relatives of SZ patients. The genetic mechanism of SZ is complex and some chromosomal regions and candidate genes have been reported by a association analysis and lnkage analysis.MTHFR(Methylenetetrahydrofolate reductase) plays an important role in carbon cycle, and provides the precursor for DNA nucleotide bases. MTHFR is also involved in membrane lipid and DNA methylation. Two single nucleotide polymorphisms(SNPs) of MTHFR, C677T(rs1801133) and A1298C(rs1801131), can lead to the change of enzyme activity and influence the concentration of homocysteine. Both the change of C677T(alanine into valine) and A1298C(glutamate into alanine) can cause decreased activity of MTHFR, especially for C677 T polymorphism. The human and animal experiments have shown that the reduction of folic acid and increasement of homocyseine could cause damage to the nervous system.ObjectiveTo investigate association between MTHFR C677T/A1298 C polymorphisms and schizophrenia in a family based studyMethodsA family-based association study comprising 103 families with schizophrenic child was constructed, and these schizophrenic were hospitalized in Shandong Mental Health Center from 2005 to 2010. These samples consist of 88 complete triads, 11 mother-child dyads and 4 father-child dyads. The cases, average age was 17±3 years and the onset was 16±3 years. The male/female ratio was 1: 1.14(48/55). Subjects were all Han Chinese from Shandong peninsula. The criteria for diagnosing schizophrenia were made according to ICD-10 Classification of Mental and Behavioural Disorders.High Resolution Melting( HRM) was used to genotype the C677 T and A1298 C polymorphisms. Transmission Disequilibrium Test(TDT) and log-linear model were applied in statistical analysis.ResultsTDT analysis showed no preferential transmission from parents heterozygous for the MTHFR C677 T and A1298 C polymorphisms to schizophrenia offspring(with C677 T locus P =0.753, A1298 C locus P =0.492). By perform log-linear model no asymmetry within parental mating type were found either in single allele(C677T P =0.415, A1298 C P =0.846)or in haplotype(P=0.607).ConclusionThe study provided no evidence that transmission of the MTHFR C677 T and A1298 C allele is associated with schizophrenia risk. In addition, no evidence that the maternal genotype influences the risk of having schizophrenia off-springs substantially.