Pettersson-Fernholm Kim, Karvonen Matti K, Kallio Jaana, Forsblom Carol M, Koulu Markku, Pesonen Ullamari, Fagerudd Johan A, Groop Per-Henrik
Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, and Folkhälsan Research Center, Biomedicum, University of Helsinki, Helsinki, Finland.
Diabetes Care. 2004 Feb;27(2):503-9. doi: 10.2337/diacare.27.2.503.
Neuropeptide Y is a potent vasoconstrictor thought to enhance the development of atherosclerosis. The leucine 7 to proline 7 (Leu7Pro) polymorphism, located in the signal peptide part of the human preproneuropeptide Y, has been associated with serum lipid levels, intima-media thickness of the common carotid arteries, and diabetic retinopathy in type 2 diabetic patients. Therefore, we investigated the impact of the Leu7Pro polymorphism on diabetic nephropathy, cardiovascular risk factors, and cardiovascular disease in type 1 diabetic patients.
A total of 996 patients from the Finnish Diabetic Nephropathy study were studied in a case-control, cross-sectional study. The carrier frequency of the Pro7 substitution was 13% in the entire study population.
The Pro7 substitution was more common in patients with proteinuria than in those with a normal albumin excretion rate (16 vs. 11%, P < 0.05). Patients with the Pro7 allele had worse glycemic control (HbA(1c) 8.8 vs. 8.5%, P < 0.005), more coronary heart disease (CHD) (14 vs. 8%, P < 0.05), and higher serum triglycerides (1.65 vs. 1.35 mmol/l, P < 0.005) than patients with the wild-type genotype. There were no differences in the plasma neuropeptide Y levels between the patients with Pro7 compared with those with the wild-type genotype. The Leu7Pro polymorphism was independently associated with HbA(1c) (P < 0.001), proteinuria (P < 0.01), and CHD (P < 0.01) in multiple regression analyses.
We conclude that the Leu7Pro polymorphism may contribute to the genetic susceptibility to diabetic nephropathy and CHD in type 1 diabetic patients, possibly by influencing glycemic control and triglycerides.
神经肽Y是一种强效血管收缩剂，被认为会促进动脉粥样硬化的发展。位于人前神经肽Y信号肽部分的亮氨酸7突变为脯氨酸7（Leu7Pro）多态性，与2型糖尿病患者的血脂水平、颈总动脉内膜中层厚度以及糖尿病视网膜病变有关。因此，我们研究了Leu7Pro多态性对1型糖尿病患者糖尿病肾病、心血管危险因素和心血管疾病的影响。
在一项病例对照横断面研究中，对来自芬兰糖尿病肾病研究的996名患者进行了研究。在整个研究人群中，Pro7替代的携带频率为13%。
与白蛋白排泄率正常的患者相比，蛋白尿患者中Pro7替代更为常见（16%对11%，P<0.05）。与野生型基因型患者相比，携带Pro7等位基因的患者血糖控制更差（糖化血红蛋白8.8%对8.5%，P<0.005），冠心病（CHD）更多（14%对8%，P<0.05），血清甘油三酯更高（1.65对1.35 mmol/l，P<0.005）。Pro7患者与野生型基因型患者的血浆神经肽Y水平没有差异。在多元回归分析中，Leu7Pro多态性与糖化血红蛋白（P<0.001）、蛋白尿（P<0.01）和冠心病（P<0.01）独立相关。
我们得出结论，Leu7Pro多态性可能通过影响血糖控制和甘油三酯水平，导致1型糖尿病患者对糖尿病肾病和冠心病的遗传易感性。
