Genetics and Molecular Biology Research Unit-UPGEM, São José do Rio Preto Medical School-FAMERP, Av. Brigadeiro Faria Lima, N masculine 5416, Bloco U-6, São José do Rio Preto, SP, 15.090-000, Brazil.
J Thromb Thrombolysis. 2010 Jan;29(1):32-40. doi: 10.1007/s11239-009-0321-7. Epub 2009 Mar 13.
Alterations in the enzymes involved in homocysteine (Hcy) metabolism or vitamin deficiency could play a role in coronary artery disease (CAD) development. This study investigated the influence of MTHFR and MTR gene polymorphisms, plasma folate and MMA on Hcy concentrations and CAD development. MMA and folate concentrations were also investigated according to the polymorphisms.
Two hundred and eighty-three unrelated Caucasian individuals undergoing coronary angiography (175 with CAD and 108 non-CAD) were assessed in a case-control study. Plasma Hcy and MMA were measured by liquid chromatography/tandem mass spectrometry. Plasma folate was measured by competitive immunoassay. Dietary intake was evaluated using a nutritional questionnaire. Polymorphisms MTHFR and MTR were investigated by polymerase chain reaction (PCR) followed by enzyme digestion or allele-specific PCR.
Hcy mean concentrations were higher in CAD patients compared to controls, but below statistical significance (P = 0.246). Increased MMA mean concentrations were frequently observed in the CAD group (P = 0.048). Individuals with MMA concentrations >0.5 micromol/l (vitamin B(12) deficiency) were found only in the CAD group (P = 0.004). A positive correlation between MMA and Hcy mean concentrations was observed in both groups, CAD (P = 0.001) and non-CAD (P = 0.020). MMA mean concentrations were significantly higher in patients with hyperhomocysteinemia in both groups, CAD and non-CAD (P = 0.0063 and P = 0.013, respectively). Folate mean concentration was significantly lower in carriers of the wild-type MTHFR 1298AA genotype (P = 0.010).
Our results suggest a correlation between the MTHFR A1298C polymorphism and plasma folate concentration. Vitamin B(12) deficiency, reflected by increased MMA concentration, is an important risk factor for the development both of hyperhomocysteinemia and CAD.
同型半胱氨酸（Hcy）代谢或维生素缺乏相关酶的改变可能在冠状动脉疾病（CAD）的发展中起作用。本研究调查了 MTHFR 和 MTR 基因多态性、血浆叶酸和 MMA 对 Hcy 浓度和 CAD 发展的影响。还根据多态性研究了 MMA 和叶酸浓度。
在一项病例对照研究中，评估了 283 名无关的白种人接受冠状动脉造影（CAD 患者 175 名，非 CAD 患者 108 名）。通过液相色谱/串联质谱法测量血浆 Hcy 和 MMA。通过竞争免疫测定法测量血浆叶酸。使用营养问卷评估膳食摄入量。通过聚合酶链反应（PCR）后酶消化或等位基因特异性 PCR 研究 MTHFR 和 MTR 多态性。
与对照组相比，CAD 患者的 Hcy 平均浓度较高，但无统计学意义（P = 0.246）。在 CAD 组中经常观察到 MMA 平均浓度升高（P = 0.048）。仅在 CAD 组中发现 MMA 浓度>0.5μmol/L（维生素 B12 缺乏）的个体（P = 0.004）。在两组（CAD 和非 CAD）中均观察到 MMA 和 Hcy 平均浓度之间存在正相关（CAD，P = 0.001；非 CAD，P = 0.020）。在两组（CAD 和非 CAD）中，高同型半胱氨酸血症患者的 MMA 平均浓度均显著升高（P = 0.0063 和 P = 0.013）。MTHFR 1298AA 野生型基因型携带者的叶酸平均浓度显著降低（P = 0.010）。
我们的结果表明 MTHFR A1298C 多态性与血浆叶酸浓度之间存在相关性。MMA 浓度升高反映的维生素 B12 缺乏是高同型半胱氨酸血症和 CAD 发展的重要危险因素。
