2型糖尿病患者载脂蛋白E基因多态性、高胆固醇血症与肾小球滤过率：一项9年随访研究

Apolipoprotein E gene polymorphism, hypercholesterolemia and glomerular filtration rate in type 2 diabetic subjects: a 9-year follow-up study.

作者信息

Lehtinen Saara, Rantalaiho Vappu, Wirta Ole, Pasternack Amos, Laippala Pekka, Koivula Timo, Lehtimäki Terho

机构信息

Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere, Finland.

出版信息

J Biomed Sci. 2003 Mar-Apr;10(2):260-5. doi: 10.1007/BF02256061.

DOI:10.1007/BF02256061

PMID:12595762

Abstract

OBJECTIVE

To study the association between apolipoprotein E (apoE) genotype and the rate of decline in glomerular filtration rate (GFR) in type 2 diabetic patients in a 9-year prospective study.

METHODS

GFR was determined in 84 type 2 diabetic patients by plasma clearance of (51)Cr-EDTA at baseline and after 9 years of follow-up. ApoE genotypes were determined by polymerase chain reaction and restriction enzyme HHAI digestion and designated as epsilon4 allele group (apoE4/2, 4/3 and 4/4 genotypes; n = 20) and non-epsilon4 allele group (apoE3/3 and E3/2 genotypes; n = 64). We focused our analysis on those patients who were more likely to progress to diabetic renal disease, i.e. whose GFR fell more than expected in the normal course of ageing [1 ml x min(-1) x (1.73 m(2))(-1) per year].

RESULTS

In the whole population, the decline in the GFR did not differ statistically significantly between the apoE genotype groups [p = 0.65 with analysis of variance for repeated variables (RANOVA) for interaction between apoE genotype group and time point]. However, among patients whose GFR changed more than 9 ml x min(-1) x (1.73 m(2))(-1), GFR showed a statistically significantly greater decline in the epsilon4 allele group (n = 11) than in the non-epsilon4 allele group (n = 43) [from 116 +/- 36 to 80 +/- 29 ml x min(-1) x (1.73 m(2))(-1) vs. from 119 +/- 20 to 96 +/- 18 ml x min(-1) x (1.73 m(2))(-1); p = 0.005 with RANOVA].

CONCLUSION

ApoE allele epsilon4 may speed up the rate of decline of the GFR in patients with progressive diabetic renal disease.

摘要

目的

在一项为期9年的前瞻性研究中，研究2型糖尿病患者载脂蛋白E（apoE）基因型与肾小球滤过率（GFR）下降速率之间的关联。

方法

通过在基线和9年随访后检测84例2型糖尿病患者血浆中（51）Cr-EDTA的清除率来测定GFR。通过聚合酶链反应和限制性内切酶HHAI消化来确定apoE基因型，并分为ε4等位基因组（apoE4/2、4/3和4/4基因型；n = 20）和非ε4等位基因组（apoE3/3和E3/2基因型；n = 64）。我们将分析重点放在那些更有可能进展为糖尿病肾病的患者身上，即其GFR在正常衰老过程中下降超过预期[每年1 ml·min-1·（1.73 m2）-1]。

结果

在整个人群中，apoE基因型组之间的GFR下降在统计学上无显著差异[p = 0.65，采用重复变量方差分析（RANOVA）分析apoE基因型组与时间点之间的相互作用]。然而，在GFR变化超过9 ml·min-1·（1.73 m2）-1的患者中，ε4等位基因组（n = 11）的GFR下降在统计学上显著大于非ε4等位基因组（n = 43）[从116±36降至80±29 ml·min-1·（1.73 m2）-1，而从119±20降至96±18 ml·min-1·（1.73 m2）-1；RANOVA分析p = 0.005]。