title: Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene with schizophrenia: association is significant in men but not in women.
abstract: Schizophrenia is a complex and common psychiatric disorder with a polygenic inheritance. In our previous report, we showed an association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and schizophrenia in patients from Bakirkoy in Istanbul, Turkey [Sazci, A., Ergul, E., Guzelhan, Y., Kaya, G., Kara, I., 2003. Methylenetetrahydrofolate reductase gene polymorphisms in patients with schizophrenia. Mol. Brain Res. 117, 104-107]. We wanted also independently to confirm this study in a gender-specific manner with schizophrenic patients from Erenkoy in Istanbul, Turkey. To investigate the role of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene in schizophrenia in a gender-specific manner, we analyzed the genotypes of MTHFR677 and MTHFR1298 of 297 schizophrenic patients and 341 healthy controls, using a polymerase chain reaction restriction fragment length polymorphism method. The MTHFR 677T allele was significantly distributed (chi2=7.312; P=0.026), between schizophrenic patients and healthy controls. The T677T genotype was overrepresented in the total schizophrenic patients (OR=1.938; 95%CI=1.133-3.315; chi2=5.996; P=0.014). Similarly, the T677T/A1298A compound genotype was the most significant one in the total schizophrenic patients (OR=2.397; 95% CI=1.327-4.330; chi2=8.821; P=0.003). The C1298C genotype was overrepresented in the total schizophrenic patients (OR=1.706; 95%CI=1.014-2.870; chi2=4.126; P=0.042). Likewise, the C677C/C1298C compound genotype was significant in the total schizophrenic patients (OR=1.689; 95%CI=0.985-2.894; chi2=3.695; P=0.055). When schizophrenic patients and healthy controls were stratified according to gender difference, the T677T genotype and T677T/A1298A compound genotype were significantly overrepresented (OR=2.184; 95% CI=1.069-4.462; chi2=4.767; P=0.029; OR=2.748; 95% CI=1.215-6.214; chi2=6.301; P=0.012, respectively) in men schizophrenic patients. However, neither the MTHFR C677T nor the A1298C polymorphisms are associated with schizophrenia in women. In conclusion, the MTHFR 677T allele and T677T, C1298C genotypes, and T677T/A1298A, C677C/C1298C compound genotypes are genetic risk factors for schizophrenia in men but not in women in a gender-specific manner.
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, University of Kocaeli, Derince, 41900, Kocaeli, Turkey. teodorob@baylorhealth.edu
authors.forename: Ali
authors.initials: A
authors.lastname: Sazci
authors.forename: Emel
authors.initials: E
authors.lastname: Ergul
authors.forename: Ismail
authors.initials: I
authors.lastname: Kucukali
authors.forename: Ihsan
authors.initials: I
authors.lastname: Kara
authors.forename: Guner
authors.initials: G
authors.lastname: Kaya
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015331:Cohort Studies; D016001:Confidence Intervals; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)