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前神经肽Y中第7位亮氨酸至第7位脯氨酸的多态性与1型糖尿病患者的蛋白尿、冠心病及血糖控制相关。

Leucine 7 to proline 7 polymorphism in the preproneuropeptide Y is associated with proteinuria, coronary heart disease, and glycemic control in type 1 diabetic patients.

作者信息

Pettersson-Fernholm Kim, Karvonen Matti K, Kallio Jaana, Forsblom Carol M, Koulu Markku, Pesonen Ullamari, Fagerudd Johan A, Groop Per-Henrik

机构信息

Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, and Folkhälsan Research Center, Biomedicum, University of Helsinki, Helsinki, Finland.

出版信息

Diabetes Care. 2004 Feb;27(2):503-9. doi: 10.2337/diacare.27.2.503.

DOI:10.2337/diacare.27.2.503
PMID:14747236
Abstract

OBJECTIVE

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.

RESEARCH DESIGN AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

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。

研究设计与方法

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%。

结果

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。

结论

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。

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