Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia.
Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia.
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DOI：
10.1093/schbul/sbt154
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发表时间：
2014-09
影响因子：
6.6
通讯作者：
Ohmori T
中科院分区：
文献类型：
--
作者：
Nishi A;Numata S;Tajima A;Kinoshita M;Kikuchi K;Shimodera S;Tomotake M;Ohi K;Hashimoto R;Imoto I;Takeda M;Ohmori T
以往的研究表明，血同型半胱氨酸水平升高和亚甲基四氢叶酸还原酶（MTHFR）C677 T多态性是精神分裂症的危险因素。然而，性别和MTHFR C677 T基因型对精神分裂症患者血同型半胱氨酸水平的影响并不一致。我们首先调查了精神分裂症患者血浆总同型半胱氨酸水平是否高于对照组，并在一个大的队列中按性别和MTHFR C677 T基因型分层（N = 1379）。其次，我们进行了一项荟萃分析的血液同型半胱氨酸水平和精神分裂症之间的关联研究，分别按性别（N = 4714）。第三，我们进行了MTHFR C677 T多态性与精神分裂症（N = 4998）之间的病例对照关联研究，并进行了基于日本受试者（N = 10 378）的遗传关联研究的荟萃分析。最后，我们评估了血浆总同型半胱氨酸水平对精神分裂症的影响，通过孟德尔随机化方法。校正年龄后的ANCOVA显示，诊断对所有分层的血浆总同型半胱氨酸水平有显著影响，随后的性别荟萃分析显示，男性和女性精神分裂症患者的血同型半胱氨酸水平升高，尽管抗精神病药物可能会影响结局。日本遗传关联研究的荟萃分析表明，MTHFR C677 T多态性与精神分裂症之间存在显著关联。日本人群中的孟德尔随机化分析得出，血浆总同型半胱氨酸每增加1-SD，精神分裂症的OR为1.15。我们的研究表明，血浆总同型半胱氨酸水平升高可能与精神分裂症的风险增加有关。
Previous studies suggest that elevated blood homocysteine levels and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism are risk factors for schizophrenia. However, the effects of gender and MTHFR C677T genotypes on blood homocysteine levels in schizophrenia have not been consistent. We first investigated whether plasma total homocysteine levels were higher in patients with schizophrenia than in controls with stratification by gender and by the MTHFR C677T genotypes in a large cohort (N = 1379). Second, we conducted a meta-analysis of association studies between blood homocysteine levels and schizophrenia separately by gender (N = 4714). Third, we performed a case-control association study between the MTHFR C677T polymorphism and schizophrenia (N = 4998) and conducted a meta-analysis of genetic association studies based on Japanese subjects (N = 10 378). Finally, we assessed the effect of plasma total homocysteine levels on schizophrenia by a mendelian randomization approach. The ANCOVA after adjustment for age demonstrated a significant effect of diagnosis on the plasma total homocysteine levels in all strata, and the subsequent meta-analysis for gender demonstrated elevated blood homocysteine levels in both male and female patients with schizophrenia although antipsychotic medication might influence the outcome. The meta-analysis of the Japanese genetic association studies demonstrated a significant association between the MTHFR C677T polymorphism and schizophrenia. The mendelian randomization analysis in the Japanese populations yielded an OR of 1.15 for schizophrenia per 1-SD increase in plasma total homocysteine. Our study suggests that increased plasma total homocysteine levels may be associated with an increased risk of schizophrenia.
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