MTHFD 1958G>A and MTR 2756A>G polymorphisms are associated with bipolar disorder and schizophrenia.
BACKGROUND
The etiology of bipolar disorder (BD) and schizophrenia is very complex. Polymorphic variants of genes encoding enzymes of the monoaminergic may be involved in development of BD and schizophrenia. Therefore, we examined the prevalence of 1958G>A polymorphism of MTHFD1 gene, encoding trifunctional folate enzyme 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1), and 2756A>G variant of methionine synthase (MTR) gene in patients with BD (n=200), schizophrenia (n=200) and in controls (n=300).


OBJECTIVE
We investigated the genotypic and allelic frequencies of MTHFD1 1958G>A (R653Q) and MTR 2756A>G (D919G) gene polymorphisms in a group of bipolar (n=200) and schizophrenic patients (n=200), as well as in controls (n=300).


METHODS
The distributon of genotypes in all groups was tested for deviation from Hardy-Weinberg equilibrium (HWE). The Pearson's chi-square (chi) test and Fisher's exact test were applied to assess differences in the genotypic and allelic (respectively) distribution between groups of patients and controls.


RESULTS
We found that MTHFD1 1958AA or 1958AG genotypes constitute risk factors for development of bipolar disorder type I (BDI) or schizophrenia with odds ratios (OR)=1.743 (95% CI=1.211-2.508; P=0.0027; P (corr)=0.0054) and 2.667 (95% CI=1.845-3.854; P=0.0001; P (corr)=0.0002), respectively. In the same groups, the MTR 2756GG or 2756AG genotypes also constitute significant risk factors in occurrence of BDI and schizophrenia with OR=1.621 (95% CI=1.130-2.326; P=0.0086; P (corr)=0.0172) and 1.556 (95% CI=1.085-2.232; P=0.0160; P (corr)=0.032), respectively. Gender classification of patients indicated significant association only of MTHFD1 1958A allele with BDI and schizophrenia in the male patients OR=1.838 (95% CI=1.114-3.031; P=0.0166; P (corr)=0.0332) and OR=3.964 (95% CI=2.358-6.663; P=0.0001 P (corr)=0.0002), respectively.


CONCLUSIONS
Since MTHFD and MTR genes are located in 14q24 and 1q43 loci, our findings support the significance of chromosomes 14q and 1q in etiopathogenesis of bipolar disorder and schizophrenia.
Kempisty
Bartosz
B
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland.
Sikora
Jacek
J
Lianeri
Margarita
M
Szczepankiewicz
Aleksandra
A
Czerski
Piotr
P
Hauser
Joanna
J
Jagodzinski
Paweł Piotr
PP
D000225:Adenine; D001714:Bipolar Disorder / Q000201:enzymology / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14; D002894:Chromosomes, Human, Pair 4; D003710:Demography; D005260:Female; D005787:Gene Frequency; D006147:Guanine; D006801:Humans; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*; D044465:White People / Q000235:genetics
D006147:Guanine; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D000225:Adenine