Association between angiotensin-converting enzyme gene polymorphisms and diabetic nephropathy:: Case-control, haplotype, and family-based study in three European populations
Association between angiotensin-converting enzyme gene polymorphisms and diabetic nephropathy:: Case-control, haplotype, and family-based study in three European populations
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DOI：
10.1681/asn.2006101102
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发表时间：
2007-04-01
影响因子：
13.6
通讯作者：
Hager-Vionnet, Nathalie
中科院分区：
文献类型：
--
作者：
Hadjadj, Samy;Tarnow, Lise;Hager-Vionnet, Nathalie
血管紧张素转换酶基因(ACE)是1型糖尿病肾病的危险因素。这个候选基因的选择得到了横断面和后续研究的支持，但没有令人信服的基于家庭的研究可用。受试者包括丹麦、芬兰和法国的1057名患者(伴或不伴肾功能衰竭的持续性蛋白尿)和1127名对照组(长期存在正常白蛋白尿的1型糖尿病患者)和532个家庭三组，包括244个有糖尿病肾病先证者和288个非糖尿病肾病先证者。对5个血管紧张素转换酶基因多态性进行了研究。在病例对照分析中，rs1800764-C、rs4311-T、插入/缺失(I/D或rs1799752)-D、rs4366-G和rs12449782-G等位基因与糖尿病肾病的风险增加有关，其等位基因优势比分别为1.11(95%可信区间1.00~1.22)、1.18(1.04~1.33)、1.13(1.02~1.23)、1.10(0.99~1.20)和1.12(1.01~1.23)。单倍型分析进一步表明，D、rs4366-G和rs12449782_G等位基因所定义的单倍型与糖尿病肾病的危险性相关。即使没有检测到对糖尿病肾病或非糖尿病先证者的显著等位基因过度传播，基于家庭的研究也提供了与病例对照分析一致的结果。在一项大型病例对照研究中，研究表明血管紧张素转换酶基因多态与糖尿病肾病相关；这一发现在一项基于家庭的关联研究中没有得到证实。该研究群体适合寻找更多的糖尿病肾病候选基因。
Angiotensin 1-converting enzyme gene (ACE) is a risk factor for diabetic nephropathy (DN) in patients with type 1 diabetes. The selection of this candidate gene is supported by cross-sectional and follow-up studies, but no convincing family-based studies are available. Recruited were 1057 patients (with DN: persistent albuminuria with or without renal failure) and 1127 control subjects (long-standing [>= 15 yr] normoalbuminuric patients with type 1 diabetes) in Denmark, Finland, and France and 532 family trios that were composed of 244 trios with DN probands and 288 trios with non-DN probands. Five ACE polmorphisms were studied. In the case-control analysis, the rs1800764-C, rs4311-T, Insertion/deletion (I/D or rs1799752)-D, rs4366-G, and rs12449782-G alleles were associated with an increased risk for DN, homogeneously across populations, with allelic odds ratios of 1.11 (95% confidence interval 1.00 to 1.22), 1.18 (1.04 to 1.33), 1.13 (1.02 to 1.23), 1.10 (0.99 to 1.20), and 1.12 (1.01 to 1.23), respectively. Haplotype analysis further demonstrated that the haplotype defined by the D, rs4366-G and rs12449782_G alleles was associated with a greater risk for DN. Even though no significant allelic overtransmission to DN or non-DN probands was detected, the family-based study provided consistent results with the case-control analysis. In a large case-control study, it was shown that the ACE polymorphisms were associated with DN; these findings were not confirmed in a family-based association study. This study population is suitable to search for additional candidate genes for DN.