Moczulski Dariusz, Fojcik Hanna, Zukowska-Szczechowska Ewa, Szydlowska Ilona, Grzeszczak Wladyslaw
Department of Internal Medicine, Diabetology and Nephrology, Silesian School of Medicine, Zabrze, Poland.
Nephrol Dial Transplant. 2003 Aug;18(8):1535-40. doi: 10.1093/ndt/gfg211.
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme of homocysteine metabolism. The C677T polymorphism of the MTHFR gene has been reported to be associated with elevated plasma homocysteine in patients with low folic acid intake. A recently reported second common polymorphism, A1298C, may increase homocysteine, but only in individuals carrying the T677 allele. This study aimed to investigate the influence of the C677T and A1298C polymorphisms of the MTHFR gene on the development of diabetic nephropathy in Caucasian patients with type 2 diabetes.
We genotyped 429 type 2 diabetic patients for the C677T and A1298C polymorphisms using standard PCR-based protocols, and divided them into three groups based on renal status: 159 patients with normoalbuminuria, 149 with microalbuminuria, and 121 with persistent proteinuria and chronic renal failure (CRF). The C677T and A1298C genotype frequencies were compared among the three groups.
Although the frequencies of the CT and TT genotypes of the C677T polymorphism tended to increase with each stage of diabetic nephropathy (53, 56 and 63% in normoalbuminuria, microalbuminuria and proteinuria/CRF, respectively), these differences were not significant. When male and female patients were analysed separately, the effect was seen only in males. The CT + TT genotype was present in 46% of male patients with normoalbuminuria, in 57% with microalbuminuria and in 68% with proteinuria/CRF (OR = 2.46; 95% CI 1.13-5.38). There were no differ-ences in the A1298C polymorphism among the three groups.
These findings indicate that the C677T polymorphism is a risk factor for diabetic nephrop-athy in male patients with type 2 diabetes.
亚甲基四氢叶酸还原酶（MTHFR）是同型半胱氨酸代谢的一种调节酶。据报道，在叶酸摄入不足的患者中，MTHFR基因的C677T多态性与血浆同型半胱氨酸水平升高有关。最近报道的第二种常见多态性A1298C可能会升高同型半胱氨酸水平，但仅在携带T677等位基因的个体中出现。本研究旨在调查MTHFR基因的C677T和A1298C多态性对高加索2型糖尿病患者糖尿病肾病发生发展的影响。
我们采用基于标准聚合酶链反应（PCR）的方法，对429例2型糖尿病患者的C677T和A1298C多态性进行基因分型，并根据肾脏状况将他们分为三组：159例正常白蛋白尿患者、149例微量白蛋白尿患者和121例持续性蛋白尿和慢性肾衰竭（CRF）患者。比较三组患者的C677T和A1298C基因型频率。
尽管C677T多态性的CT和TT基因型频率倾向于随着糖尿病肾病的每个阶段而增加（正常白蛋白尿、微量白蛋白尿和蛋白尿/CRF患者中分别为53%、56%和63%），但这些差异并不显著。当分别分析男性和女性患者时，这种影响仅在男性中可见。CT + TT基因型在46%的正常白蛋白尿男性患者、57%的微量白蛋白尿男性患者和68%的蛋白尿/CRF男性患者中出现（比值比=2.46；95%可信区间1.13 - 5.一、38）。三组患者的A1298C多态性没有差异。
这些发现表明，C677T多态性是2型糖尿病男性患者发生糖尿病肾病的一个危险因素。
