载脂蛋白M启动子多态性改变启动子活性并赋予1型糖尿病发生的易感性。

Apolipoprotein M promoter polymorphisms alter promoter activity and confer the susceptibility to the development of type 1 diabetes.

作者信息

Wu Xiaopan, Niu Nifang, Brismar Kerstin, Zhu Xilin, Wang Xin, Efendic Suad, Du Te, Liu Yang, Gu Harvest F, Liu Ying

机构信息

National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 5 Dongdan 3 Tiao, Beijing 100005, PR China.

出版信息

Clin Biochem. 2009 Jan;42(1-2):17-21. doi: 10.1016/j.clinbiochem.2008.10.008. Epub 2008 Oct 30.

DOI:10.1016/j.clinbiochem.2008.10.008

PMID:19007767

Abstract

OBJECTIVES

Apolipoprotein M plays an important role in the formation of prebeta-HDL and cholesterol efflux to HDL. In the present study, we investigate the potential association between the ApoM promoter polymorphisms and type 1 diabetes.

DESIGN AND METHODS

The study was conducted in Peking Union Medical College, Beijing, China and Karolinska Institutet, Stockholm, Sweden. Two populations, including 493 Han Chinese subjects (177 T1D patients/316 controls) and 225 Swedish (124/101), are enrolled in the present study. Three single nucleotide polymorphisms (SNP) C-1065A, T-855C and T-778C in the promoter region of the ApoM gene are genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. Promoter activity was measured by reporter gene assay.

RESULTS

SNP T-778C was strongly associated with T1D in both Han Chinese (p=0.002, OR=2.188, CI 95%=1.338-3.581) and Swedish (p=0.021, OR=2.865, CI 95%=1.128-7.278) populations. The luciferase activity of -778C promoter was 1.41 times as high as that of -778T promoter (9.90+/-1.92 vs. 7.04+/-0.76, p=0.001).

CONCLUSIONS

Allele C of SNP T-778C may increase promoter activity and confer the risk susceptibility to the development of T1D.

摘要

目的

载脂蛋白M在前β-HDL的形成以及胆固醇向HDL的流出过程中发挥重要作用。在本研究中，我们调查了载脂蛋白M启动子多态性与1型糖尿病之间的潜在关联。

设计与方法

本研究在中国北京的北京协和医学院和瑞典斯德哥尔摩的卡罗林斯卡学院进行。本研究纳入了两个人群，包括493名汉族受试者（177例1型糖尿病患者/316例对照）和225名瑞典人（124/101）。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对载脂蛋白M基因启动子区域的三个单核苷酸多态性（SNP）C-1065A、T-855C和T-778C进行基因分型。通过报告基因测定法测量启动子活性。

结果

SNP T-778C在汉族人群（p=0.002，OR=2.188，95%CI=1.338-3.581）和瑞典人群（p=0.021，OR=2.865，95%CI=1.128-7.278）中均与1型糖尿病密切相关。-778C启动子的荧光素酶活性是-778T启动子的1.41倍（9.90±1.92对7.04±0.76，p=0.001）。