Laboratory of Biochemistry-Toxicology, Monastir University Hospital, Monastir, Tunisia.
Psychiatry Clin Neurosci. 2011 Dec;65(7):664-71. doi: 10.1111/j.1440-1819.2011.02284.x.
The aim of the present study was to investigate hyperhomocysteinemia in Tunisian bipolar I patients according to 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism.
The subjects consisted of 92 patients with bipolar I disorder diagnosed according to DSM-IV, and 170 controls. Plasma total homocysteine, folate and vitamin B12 were measured. MTHFR C677T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism.
Compared with controls, patients had a significantly higher homocysteine level (16.4 ± 9.8 vs 9.6 ± 4.5 µmol/L; P < 0.001) and a significantly lower folate level (3.2 ± 0.9 vs 6.5 ± 3.2 µg/L; P < 0.001). C677T MTHFR polymorphism genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for MTHFR C677T genotypes, hypofolatemia, hypovitamin B12 and for potential confounding factors, the odds ratio (OR) of hyperhomocysteinemia associated with bipolar disorder remained significant (OR, 5.53; 95% confidence interval: 1.92-15.86; P = 0.001). In patients, there was no significant change in hyperhomocysteinemia, hypofolatemia and hypovitamin B12 with regard to the clinical and therapeutic characteristics, whereas the highest prevalence of hyperhomocysteinemia was found in depressive patients and when illness duration was >12 years. Hypofolatemia was seen in all patients on lithium and in the majority of patients on carbamazepine, and the highest prevalence of hypovitamin B12 was noted in patients taking carbamazepine.
Hyperhomocysteinemia was more frequent in bipolar I patients independent of C677T polymorphism. Patients had reduced levels of folate, which modulates homocysteine metabolism. Indeed, this finding indicates that folate supplementation may be appropriate for bipolar patients with hyperhomocysteinemia.
本研究旨在探讨 5,10-亚甲基四氢叶酸还原酶(MTHFR)C677T 多态性与突尼斯双相 I 型患者高同型半胱氨酸血症的关系。
研究对象包括 92 例根据 DSM-IV 诊断为双相 I 型障碍的患者和 170 例对照。检测血浆总同型半胱氨酸、叶酸和维生素 B12。MTHFR C677T 多态性通过聚合酶链反应-限制性片段长度多态性确定。
与对照组相比,患者的同型半胱氨酸水平明显升高(16.4±9.8 vs 9.6±4.5µmol/L;P<0.001),叶酸水平明显降低(3.2±0.9 vs 6.5±3.2µg/L;P<0.001)。C677T MTHFR 多态性基因型频率符合 Hardy-Weinberg 平衡。在调整 MTHFR C677T 基因型后,低叶酸血症、低维生素 B12 和潜在混杂因素后,双相障碍相关高同型半胱氨酸血症的优势比(OR)仍具有显著性(OR,5.53;95%置信区间:1.92-15.86;P=0.001)。在患者中,高同型半胱氨酸血症、低叶酸血症和低维生素 B12 与临床和治疗特征无关,而抑郁患者和疾病持续时间>12 年的患者高同型半胱氨酸血症的患病率最高。锂治疗的所有患者均出现低叶酸血症,卡马西平治疗的大多数患者出现低叶酸血症,服用卡马西平的患者维生素 B12 缺乏的患病率最高。
无论 C677T 多态性如何,双相 I 型患者高同型半胱氨酸血症更为常见。患者的叶酸水平降低,而叶酸可以调节同型半胱氨酸代谢。因此,这一发现表明,补充叶酸可能对高同型半胱氨酸血症的双相患者有益。