University of Aleppo, Department of Analytical Chemistry, Faculty of Pharmacy, Aleppo, Syria.
Asian J Psychiatr. 2012 Jun;5(2):144-9. doi: 10.1016/j.ajp.2012.03.002. Epub 2012 Apr 26.
The folate-homocystiene metabolic pathway has been shown to be involved in the susceptibility for developing schizophrenia by several studies. In the present study we investigated the role of three common polymorphisms of the folate-homocysteine metabolic pathway in an Arab population from Syria consisting of 85 schizophrenic patients and 126 healthy controls. The studied polymorphisms included the MTHFR C677T and A1298C, and MTRR A66G, all of which result into amino acid changes, and were previously shown to yield decreased enzymatic activity and alter plasma homocysteine concentration. While MTHFR C677T and A1298C polymorphisms were not previously studied in an Arab population with respect to the susceptibility for developing schizophrenia, the MTRR A66G was not previously investigated in any population around the world. Our results indicated a strong association between MTHFR A1298C and schizophrenia. The variant C allele frequency was significantly higher in the patients group (40% vs 29.4%, OR=1.6, 95% CI (1.06-2.41), p=0.023). A statistically significant association was found for MTHFR 677TT genotype under the recessive model in the male patients subgroup (OR=2.6, 95% CI (1.04-6.5), p=0.036), and MTHFR 677CT genotype under the overdominant model in the total patients group (OR=0.52 95% CI (0.29-0.92), p=0.024). No statistically significant association was found for MTRR A66G polymorphism on an individual basis. However, a borderline association was found for the CC/GG (C677T/A66G) compound genotype (OR=2.24, 95% CI (0.97-5.15), p=0.053). Our results support the hypothesis of association between schizophrenia and folate-homocystiene metabolic pathway genes.
叶酸-同型半胱氨酸代谢途径已被多项研究表明与精神分裂症的易感性有关。在本研究中，我们研究了叶酸-同型半胱氨酸代谢途径中三个常见多态性在一个由 85 名精神分裂症患者和 126 名健康对照组成的叙利亚阿拉伯人群中的作用。所研究的多态性包括 MTHFR C677T 和 A1298C 以及 MTRR A66G，所有这些多态性都导致氨基酸变化，并且先前已经显示出降低的酶活性并改变血浆同型半胱氨酸浓度。虽然 MTHFR C677T 和 A1298C 多态性在关于精神分裂症易感性的阿拉伯人群中以前没有研究过，但 MTRR A66G 在世界上任何人群中都没有被研究过。我们的结果表明，MTHFR A1298C 与精神分裂症之间存在强烈的关联。在患者组中，变体 C 等位基因频率显着升高（40%对 29.4%，OR=1.6，95%CI（1.06-2.41），p=0.023）。在男性患者亚组中，在隐性模型下，MTHFR 677TT 基因型存在统计学显着关联（OR=2.6，95%CI（1.04-6.5），p=0.036），在总患者组中，在超显性模型下，MTHFR 677CT 基因型存在统计学显着关联（OR=0.52，95%CI（0.29-0.92），p=0.024）。MTRR A66G 多态性在个体基础上没有统计学显着关联。然而，对于 CC/GG（C677T/A66G）复合基因型，存在边缘关联（OR=2.24，95%CI（0.97-5.15），p=0.053）。我们的结果支持精神分裂症与叶酸-同型半胱氨酸代谢途径基因之间存在关联的假设。
