Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: A Dutch population based case-control study
Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: A Dutch population based case-control study
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DOI：
10.1002/ajmg.b.30179
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发表时间：
2005-05-05
影响因子：
2.8
通讯作者：
Blom, HJ
中科院分区：
文献类型：
--
作者：
Muntjewerff, JW;Hoogendoorn, MLC;Blom, HJ
精神分裂症病因中同型半胱氨酸代谢异常参与的证据有限且存在争议。进行了一项病例对照研究，以量化荷兰血统受试者中同型半胱氨酸浓度升高或亚甲基四氢叶酸还原酶 (MTHFR) 基因 677C -> T 多态性 (677TT) 纯合性的情况下患精神分裂症的风险。我们确定了 254 名明确的患者和 414 名健康对照者的 677C -> T MTHFR 基因型分布。研究人员测量了 62 名精神分裂症患者和 432 名对照受试者的血浆同型半胱氨酸浓度。当同型半胱氨酸浓度分层为对照分布的四分位数时，我们计算出第四和第三四分位数与最低四分位数相比精神分裂症的风险增加[比值比 (OR) = 3.3； 95% 置信区间 (CI)：1.2-9.2，OR = 3.1； 95% CI：分别为 1.2-8.0]。观察到同型半胱氨酸水平增加和精神分裂症风险增加之间存在显着的剂量反应关系（P = 0.036）。 677TT 基因型与精神分裂症的 OR 为 1.6 [95% CI: 0.96-2.8] 相关。与 677CC 受试者相比，T 等位基因的杂合性 OR 为 1.3 [95% CI：0.91-1.8]。同型半胱氨酸水平升高和 MTHFR 677TT 基因型与精神分裂症风险增加相关。这些观察结果支持同型半胱氨酸代谢紊乱与精神分裂症之间的因果关系。 (c) 2005 年 Wiley-Liss, Inc.
Evidence for an involvement of aberrant homocysteine metabolism in the aetiology of schizophrenia is limited and controversial. A case-control study was performed to quantify the risk of schizophrenia in the presence of elevated homocysteine concentrations or homozygosity for the 677C -> T polymorphism (677TT) in the methylenetetrahydrofolate reductase (MTHFR) gene in subjects of Dutch ancestry. We determined the 677C -> T MTHFR genotype distribution in 254 well-defined patients and 414 healthy controls. Plasma homocysteine concentrations were measured in 62 patients with schizophrenia and 432 control subjects. When homocysteine concentrations were stratified into quartiles of the control distribution, we calculated an increased risk for schizophrenia in the fourth and third quartile versus the lowest quartile [odds ratio (OR) = 3.3; 95% confidence interval (CI): 1.2-9.2, and OR = 3.1; 95% CI: 1.2-8.0, respectively]. A significant dose-response relation of increasing homocysteine levels and increasing risk for schizophrenia was observed (P = 0.036). The 677TT genotype was associated with an OR of 1.6 [95% CI: 0.96-2.8] of having schizophrenia. Heterozygosity for the T allele compared to 677CC subjects accounted for an OR of 1.3 [95% CI: 0.91-1.8]. Elevated homocysteine levels and the MTHFR 677TT genotype are associated with an increased risk for schizophrenia. These observations support a causal relation between disturbed homocysteine metabolism and schizophrenia. (c) 2005 Wiley-Liss, Inc.