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Additive effect of MTHFR and GRIN1 genetic polymorphisms on the risk of schizophrenia

机译:MTHFR和GRIN1基因多态性对精神分裂症风险的累加作用

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摘要

Schizophrenia is a complex disorder with polygenic inheritance. The MTHFR gene (OMIM: 607093) plays an important role in the folate metabolism. It has been suggested that C677T (rs1801133) and A1298C (rs1801131) genetic polymorphisms in the MTHFR gene lead to the decreased activity of the methylenetetrahydrofolate reductase enzyme which may have significant effect on developing schizophrenia. We used a case-control study to establish the possible association between the C677T and the A1298C polymorphisms and susceptibility to schizophrenia in an Iranian population. The genotypes of the polymorphisms were determined using PCR-RFLP. The data were analyzed by logistic regression model. Data analysis revealed that the combination genotypes of 677CT/1298AA, 677CC/1298CC, 677TT/1298AA, 677CT/1298AC and 677CT/1298CC increase the risk of schizophrenia. In order to evaluate the effect of combined genotypes of the three mentioned polymorphic loci, the frequencies of the compound genotypes were compared between control and patient groups (Table 4). Base on the results, the existence of >4 risk factors showed about 32-fold increased risk for schizophrenia (OR=32.3, 95% CI: 5.52-188, P=<0.001).
机译:精神分裂症是一种具有多基因遗传的复杂疾病。 MTHFR基因(OMIM:607093)在叶酸代谢中起重要作用。有人提出,MTHFR基因中的C677T(rs1801133)和A1298C(rs1801131)遗传多态性导致亚甲基四氢叶酸还原酶的活性降低,这可能对精神分裂症的发生有重要影响。我们使用病例对照研究建立了C677T和A1298C多态性与伊朗人群中精神分裂症易感性之间的可能联系。使用PCR-RFLP确定多态性的基因型。通过逻辑回归模型分析数据。数据分析显示,677CT / 1298AA,677CC / 1298CC,677TT / 1298AA,677CT / 1298AC和677CT / 1298CC的组合基因型增加了精神分裂症的风险。为了评估上述三个多态性基因座的组合基因型的影响,比较了对照组和患者组的复合基因型频率(表4)。根据结果​​,> 4个危险因素的存在表明精神分裂症风险增加约32倍(OR = 32.3,95%CI:5.52-188,P = <0.001)。

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