Kempisty Bartosz, Sikora Jacek, Lianeri Margarita, Szczepankiewicz Aleksandra, Czerski Piotr, Hauser Joanna, Jagodzinski Paweł Piotr
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland.
Psychiatr Genet. 2007 Jun;17(3):177-81. doi: 10.1097/YPG.0b013e328029826f.
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).
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).
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.
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.
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.
双相情感障碍（BD）和精神分裂症的病因非常复杂。编码单胺能酶的基因多态性变体可能参与BD和精神分裂症的发生发展。因此，我们检测了编码三功能叶酸酶5,10-亚甲基四氢叶酸脱氢酶、5,10-亚甲四氢叶酸环水解酶和10-甲酰四氢叶酸合成酶（MTHFD1）的MTHFD1基因1958G>A多态性，以及蛋氨酸合成酶（MTR）基因2756A>G变体在BD患者（n=200）、精神分裂症患者（n=200）和对照组（n=300）中的发生率。
我们研究了一组双相情感障碍患者（n=200）、精神分裂症患者（n=200）以及对照组（n=300）中MTHFD1基因1958G>A（R653Q）和MTR基因2756A>G（D919G）多态性的基因型和等位基因频率。
检测所有组中基因型的分布是否偏离哈迪-温伯格平衡（HWE）。应用Pearson卡方（χ）检验和Fisher精确检验分别评估患者组和对照组之间基因型和等位基因分布的差异。
我们发现MTHFD1基因1958AA或1958AG基因型分别构成I型双相情感障碍（BDI）或精神分裂症发生发展的危险因素，比值比（OR）分别为1.743（95%可信区间[CI]=1.211-2.508；P=0.0027；校正P=0.0054）和2.667（95%CI=1.845-3.854；P=0.0001；校正P=0.0002）。在同一组中，MTR基因2756GG或2756AG基因型也分别构成BDI和精神分裂症发生的显著危险因素，OR分别为1.621（95%CI=1.130-2.326；P=0.0086；校正P=0.0172）和1.556（95%CI=1.085-2.232；P=0.0160；校正P=0.032）。对患者进行性别分类后发现，仅MTHFD1基因1958A等位基因在男性BDI患者和精神分裂症患者中存在显著关联，OR分别为1.838（95%CI=1.114-3.031；P=0.0166；校正P=0.0332）和3.964（95%CI=2.358-6.663；P=0.0001；校正P=0.0002）。
由于MTHFD和MTR基因分别位于14q24和1q43位点，我们的研究结果支持14号染色体和1号染色体在双相情感障碍和精神分裂症病因学中的重要性。
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