Sheffield Hallam University, Sheffield, UK.
ZhongDa Hospital and SouthEast University, Nanjing, China.
Int J Neuropsychopharmacol. 2014 Mar;17(3):485-90. doi: 10.1017/S1461145713001375. Epub 2013 Nov 13.
Genetic variants of the methylenetetrahydrofolate reductase (MTHFR) gene involved in homocysteine metabolism may be important predictors of antipsychotic drug-induced weight gain (AIWG). We tested whether two functional MTHFR polymorphisms are related to AIWG. Weight gain was studied in two cohorts of first-episode, initially drug-naive schizophrenia patients; Chinese Han (n = 182) and Spanish Caucasians (n = 72) receiving antipsychotics for 10 wk and 3 months respectively. Blood DNA was genotyped for 677C/T and 1298A/C MTHFR polymorphisms. Patients with the 677 CC genotype had a significantly greater increase in BMI compared to T-allele carriers in both Chinese (p = 0.012) and Spanish (p = 0.017) samples. The 677C/T MTHFR polymorphism showed an additive effect, but no significant interaction, with the -759C/T HTR2C polymorphism previously associated with AIWG. These results suggest that the 677C/T MTHFR polymorphism might, along with the -759C/T HTR2C polymorphism and other genetic factors, provide a useful marker for the important and limiting side effect of AIWG.
参与同型半胱氨酸代谢的亚甲基四氢叶酸还原酶（MTHFR）基因的遗传变异可能是抗精神病药引起体重增加（AIWG）的重要预测因子。我们测试了两个功能性 MTHFR 多态性是否与 AIWG 有关。体重增加在两个首次发作、最初未接受药物治疗的精神分裂症患者队列中进行了研究；中国汉族（n = 182）和西班牙白种人（n = 72）分别接受抗精神病药物治疗 10 周和 3 个月。对 677C/T 和 1298A/C MTHFR 多态性进行了血 DNA 基因分型。与 T 等位基因携带者相比，677CC 基因型的患者在中国（p = 0.012）和西班牙（p = 0.017）两个样本中 BMI 的增加明显更大。677C/T MTHFR 多态性显示出累加效应，但与先前与 AIWG 相关的 -759C/T HTR2C 多态性无显著交互作用。这些结果表明，677C/T MTHFR 多态性可能与 -759C/T HTR2C 多态性和其他遗传因素一起，为 AIWG 的重要且限制副作用提供了有用的标志物。
