Hadjadj S, Gallois Y, Simard G, Bouhanick B, Passa P, Grimaldi A, Drouin P, Tichet J, Marre M
Médecine B, University Hospital, Angers, France.
Nephrol Dial Transplant. 2000 Dec;15(12):1971-6. doi: 10.1093/ndt/15.12.1971.
Genetic susceptibility contributes to the risk of diabetic nephropathy. Lipid disorders may favour diabetic nephropathy. Thus polymorphisms in lipid metabolism are candidates for the genetic component of risk for diabetic nephropathy.
We searched for a contribution of the genetic polymorphisms of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and apolipoprotein epsilon (Apo E) to the development of diabetic nephropathy by studying 494 type 1 diabetic patients with proliferative retinopathy and various stages of diabetic nephropathy (GENEDIAB Study). The selection process ensured that all patients had expressed their risk of chronic complications due to uncontrolled diabetes. Thus the nephropathy stages were largely influenced by genetic background. The lipid profile included fasting plasma total cholesterol (TC), triglycerides (TG), apolipoprotein A1 (Apo A1) and B (Apo B), and lipoprotein (a) (Lp(a)). Genetic polymorphisms were determined by PCR-based detection of Apo epsilon (e2/e3/e4), LPL (mutation Asn 291 Ser) and CETP (TAQ:IB B1/B2).
One hundred and fifty-seven patients (32%) had no nephropathy, 104 (21%) incipient nephropathy, 126 (25%) established nephropathy and 107 (22%) advanced nephropathy. There was a significant relationship between the stages of diabetic nephropathy and TC (P=0.002), TG (P<0.0001), Apo B (P=0.0007) or Lp(a) (P=0. 038), but not Apo A1. However the genetic polymorphism distributions of LPL, CETP and Apo epsilon did not differ in terms of renal complications. The study power to reject the null hypothesis was 58% for the Apo epsilon genotypes.
These results support no or only marginal effects of a genetic basis for lipid disturbances encountered in diabetic nephropathy.
遗传易感性会增加患糖尿病肾病的风险。脂质紊乱可能会促使糖尿病肾病的发生。因此，脂质代谢中的多态性是糖尿病肾病风险遗传因素的候选对象。
我们通过研究494例患有增殖性视网膜病变及处于糖尿病肾病不同阶段的1型糖尿病患者（GENEDIAB研究），探寻脂蛋白脂肪酶（LPL）、胆固醇酯转运蛋白（CETP）和载脂蛋白ε（Apo E）的基因多态性对糖尿病肾病发展的影响。选择过程确保所有患者都因糖尿病控制不佳而表现出慢性并发症的风险。因此，肾病阶段在很大程度上受遗传背景的影响。血脂谱包括空腹血浆总胆固醇（TC）、甘油三酯（TG）、载脂蛋白A1（Apo A1）和B（Apo B）以及脂蛋白（a）[Lp（a）]。基因多态性通过基于聚合酶链反应（PCR）的方法检测Apo ε（e2/e3/e4）、LPL（Asn 291 Ser突变）和CETP（TAQ：IB B1/B2）来确定。
157例患者（32%）无肾病，104例（21%）为早期肾病，126例（25%）为确诊肾病，107例（22%）为晚期肾病。糖尿病肾病各阶段与TC（P = 0.002）、TG（P < 0.0001）、Apo B（P = 0.0007）或Lp（a）（P = 0.038）之间存在显著关系，但与Apo A1无关。然而，LPL、CETP和Apo ε的基因多态性分布在肾脏并发症方面并无差异。对于Apo ε基因型，拒绝原假设的检验效能为58%。
这些结果支持糖尿病肾病中脂质紊乱的遗传基础不存在或仅有微小影响。
