Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, PO box 616, 6200 MD Maastricht, The Netherlands.
Schizophr Res. 2010 Aug;121(1-3):193-8. doi: 10.1016/j.schres.2010.05.030. Epub 2010 Jun 12.
Meta-analyses have implicated polymorphisms in MTHFR, encoding a critical enzyme in folate and homocysteine metabolism, in both schizophrenia and CVD.
A possible association between the C677T and A1298C polymorphisms of the MTHFR gene on the one hand, and metabolic syndrome on the other, was examined in a naturalistic cohort of 518 patients with a schizophrenia spectrum disorder screened for metabolic disturbances at the Catholic University of Louvain, Belgium.
MTHFR A1298C, but not C677T, was associated with the metabolic syndrome, C/C genotypes having a 2.4 times higher risk compared to A/A genotypes (95% CI 1.25-4.76, p=0.009). Haplotype analysis revealed similar findings, showing greater risk for metabolic syndrome associated with the 677C/1298C haplotype compared to the reference 677C/1298A haplotype (OR 1.72, 95% CI 1.24-2.39, p=0.001). These associations were not explained by circulating folate levels. Differences between A1298C genotype groups were considerably greater in the subsample treated with clozapine or olanzapine (OR C/C versus A/A 3.87, 95% CI 1.51-9.96) than in subsample treated with any of the other antipsychotics (OR C/C versus A/A 1.30, 95% CI 0.47-3.74), although this did not formally reach statistical significance in the current cross-sectional study (gene-by-group interaction chi(2)=3.0, df=1, p=0.08).
These data provide evidence supporting an association between MTHFR and risk of metabolic syndrome in patients with schizophrenia. Prospective studies evaluating the course of metabolic outcomes after initiation of antipsychotic medication are needed to evaluate possible gene-by-treatment interaction more specifically.
荟萃分析表明，编码叶酸和同型半胱氨酸代谢关键酶的 MTHFR 基因中的多态性与精神分裂症和心血管疾病（CVD）都有关。
在比利时天主教鲁汶大学对代谢紊乱进行筛查的精神分裂症谱系障碍患者自然队列中，研究了 MTHFR 基因的 C677T 和 A1298C 多态性与代谢综合征之间的可能关联。
MTHFR A1298C 而非 C677T 与代谢综合征相关，C/C 基因型的风险比 A/A 基因型高 2.4 倍（95%CI 1.25-4.76，p=0.009）。单体型分析也得到了相似的结果，表明与参考 677C/1298A 单体型相比，代谢综合征相关的 677C/1298C 单体型风险更高（OR 1.72，95%CI 1.24-2.39，p=0.001）。这些关联不能用循环叶酸水平来解释。在接受氯氮平或奥氮平治疗的亚组中，A1298C 基因型组之间的差异明显大于接受任何其他抗精神病药物治疗的亚组（OR C/C 与 A/A 3.87，95%CI 1.51-9.96），尽管在当前的横断面研究中，这并未正式达到统计学意义（基因-组间交互作用 χ2=3.0，df=1，p=0.08）。
这些数据提供了支持 MTHFR 与精神分裂症患者代谢综合征风险之间关联的证据。需要前瞻性研究来评估抗精神病药物治疗后代谢结果的病程，以更具体地评估可能的基因-治疗相互作用。
