Delport Darnielle, Schoeman Renata, van der Merwe Nicole, van der Merwe Lize, Fisher Leslie R, Geiger Dieter, Kotze Maritha J
Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Metab Brain Dis. 2014 Jun;29(2):377-84. doi: 10.1007/s11011-014-9506-7. Epub 2014 Feb 18.
Low folate intake in the presence of the functional MTHFR 677 C > T (rs1801133) polymorphism is an important cause of elevated homocysteine levels previously implicated in major depressive disorder (MDD) and many other chronic diseases. In this study the clinical relevance and inter-relationship of these aspects were evaluated in 86 South African patients diagnosed with MDD and 97 population-matched controls participating in a chronic diseases screening program. A questionnaire-based clinical and nutrition assessment was performed, homocysteine levels determined, and all study participants genotyped for MTHFR 677 C > T (rs1801133) using allele-specific TaqMan technology. The folate score was found to be significantly lower in the patient group compared to controls (p = 0.003) and correlated with increased body mass index (BMI), particularly in females with MDD (p = 0.009). BMI was significantly higher in the MDD patients compared with controls after adjustment for age and sex (p = 0.015), but this association was no longer significant after further adjustment for the level of folate intake in the diet. In MDD patients but not controls, the minor T-allele of MTHFR 677 C > T was associated with increased BMI (p = 0.032), which in turn correlated significantly with increased homocysteine levels. The significant association between BMI and homocysteine levels was observed in both the MDD patient (p = 0.049) and control (p = 0.018) study groups. The significantly higher homocysteine levels observed in MDD patients compared to controls after adjustment for age and sex (p = 0.030), therefore appears to be mediated by the effects of MTHFR 677 C > T and low folate intake on BMI. Detection of the low-penetrance MTHFR 677 C > T mutation reinforces the importance of folate intake above the recommended daily dose to prevent or restore dysfunction of the methylation pathway.
在存在功能性亚甲基四氢叶酸还原酶（MTHFR）677C>T（rs1801133）基因多态性的情况下，低叶酸摄入量是同型半胱氨酸水平升高的一个重要原因，此前已有研究表明同型半胱氨酸水平升高与重度抑郁症（MDD）及许多其他慢性疾病有关。在本研究中，对86名被诊断为MDD的南非患者和97名参与慢性病筛查项目的、与总体人群匹配的对照者，评估了这些因素的临床相关性及相互关系。进行了基于问卷的临床和营养评估，测定了同型半胱氨酸水平，并使用等位基因特异性TaqMan技术对所有研究参与者的MTHFR 677C>T（rs1801133）进行基因分型。结果发现，与对照组相比，患者组的叶酸评分显著更低（p = 0.003），且与体重指数（BMI）增加相关，尤其是患有MDD的女性（p = 0.009）。在对年龄和性别进行校正后，MDD患者的BMI显著高于对照组（p = 0.015），但在对饮食中叶酸摄入量水平进行进一步校正后，这种关联不再显著。在MDD患者而非对照组中，MTHFR 677C>T的次要T等位基因与BMI增加相关（p = 0.032），而BMI增加又与同型半胱氨酸水平显著升高相关。在MDD患者（p = 0.049）和对照组（p = 0.018）研究组中，均观察到BMI与同型半胱氨酸水平之间存在显著关联。在对年龄和性别进行校正后，MDD患者的同型半胱氨酸水平显著高于对照组（p = 0.030），因此，这似乎是由MTHFR 677C>T和低叶酸摄入量对BMI的影响所介导的。检测到低外显率的MTHFR 677C>T突变，强化了摄入高于推荐日剂量的叶酸以预防或恢复甲基化途径功能障碍的重要性。
