Poduri Aruna, Mukherjee Debabrata, Sud Kamal, Kohli Harbir Singh, Sakhuja Vinay, Khullar Madhu
Department of Experimental Medicine & Biotechnology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India.
Mol Cell Biochem. 2008 Jan;308(1-2):43-50. doi: 10.1007/s11010-007-9610-7. Epub 2007 Sep 25.
The methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism has been shown to be associated with cardiovascular disease and in patients with end-stage renal disease (ESRD). However, the relationship between MTHFR polymorphisms and cardiovascular disease (CVD) in patients on hemodialysis has not been examined. The aim of this study was to assess the association of polymorphisms of MTHFR gene with homocysteine (Hcy) and intimal medial thickness (IMT) in patients on hemodialysis. We performed case-control study involving107 patients with ESRD and 103 healthy controls. Plasma Hcy was measured in all the subjects and these subjects were genotyped for three MTHFR polymorphisms (C677T, A1298C, and G1793A). We observed significantly higher Hcy levels in patients as compared to controls. The frequency of MTHFR 1298CC genotype was significantly higher in ESRD patients than in controls (21.4% vs. 2.9%); the frequency of the MTHFR C677T genotypes did not differ between groups (26.1% vs. 17.4%). Compound heterozygous MTHFR 677CT/1298AC genotypes showed maximum association with the risk of ESRD (OR: 12.8; 5%CI: 1.64-10.01, P < 0.05). Concurrent occurrence of MTHFR 677CC wild genotype with either 1298CC or 1793GA significantly increased the risk of disease (OR: 7.20; 95%CI: 2.06-2.51, P < 0.001 and OR: 7.60; 95%CI: 1.68-34.35; P < 0.05, respectively). MTHFR 1298CC genotype was associated with higher Hcy levels. IMT was also significantly higher in patients with the 1298CC genotype (P < 0.05). Thus, A1298C polymorphism of MTHFR gene appears to be associated with the severity of carotid atherosclerosis and co-occurrence of MTHFR polymorphisms may be a risk factor for CVD in patients on hemodialysis.
亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性已被证明与心血管疾病以及终末期肾病（ESRD）患者有关。然而，尚未研究MTHFR基因多态性与血液透析患者心血管疾病（CVD）之间的关系。本研究的目的是评估血液透析患者中MTHFR基因多态性与同型半胱氨酸（Hcy）及内膜中层厚度（IMT）之间的关联。我们进行了一项病例对照研究，纳入了107例ESRD患者和103名健康对照者。对所有受试者测量血浆Hcy，并对这三种MTHFR基因多态性（C677T、A1298C和G1793A）进行基因分型。我们观察到患者的Hcy水平显著高于对照组。ESRD患者中MTHFR 1298CC基因型的频率显著高于对照组（21.4%对2.9%）；MTHFR C677T基因型的频率在两组之间无差异（26.1%对17.4%）。复合杂合MTHFR 677CT/1298AC基因型与ESRD风险的关联最大（OR：12.8；5%CI：1.64 - 10.01，P < 0.05）。MTHFR 677CC野生基因型与1298CC或1793GA同时出现显著增加了疾病风险（OR：7.20；95%CI：2.06 - 2.51，P < 0.001和OR：7.60；95%CI：1.68 - 34.35；P < 0.05，分别）。MTHFR 1298CC基因型与较高的Hcy水平相关。1298CC基因型患者的IMT也显著更高（P < 0.05）。因此，MTHFR基因的A1298C多态性似乎与颈动脉粥样硬化的严重程度相关，MTHFR基因多态性的同时出现可能是血液透析患者CVD的一个危险因素。
