RANTES基因启动子多态性与2型糖尿病并发肾病的相关性

背景:遗传易感性是糖尿病肾病发生发展的一个重要因素。单核细胞在肾脏组织的聚集、向巨噬细胞的分化和某些趋化性细胞因子信号的增强可能与2型糖尿病肾病的发生和发展有着密切的联系。T细胞活化后表达和分泌的调节蛋白RANTES是一种C-C亚族的趋化因子,它可以介导炎性细胞的浸润和活化,引起肾小球和肾间质的损伤,这可能是糖尿病发生发展的一个重要机制。因此,RANTES基因也可能是糖尿病肾病的候选基因。目的:分析RANTES基因启动子-28C/G多态性与中国人2型糖尿病并发肾病之间的关系。设计:病例-对照观察。单位:贵阳医学院附属医院内分泌科,贵州省糖尿病中心。对象:选择2003-09/2005-09在贵阳医学院附属医院和贵州省人民医院内分泌科住院的2型糖尿病患者143例,其中正常白蛋白尿患者53例、合并微量白蛋白尿患者54例,合并大量白蛋白尿患者36例。以及来自贵阳医学院附属医院体检中心的健康对照者55例。方法:所有受试者取外周静脉血3～5mL,应用聚合酶链反应限制性片段长度多态性技术,检测RANTES基因启动子-28C/G基因型。主要观察指标:①各组人群的RANTES基因启动子-28C/G的等位基因频率和基因型频率。②采用Logistic回归分析法分析糖尿病肾病的危险因素。结果:198例受试者全部进入结果分析。①-28C/G的CG基因型频率比较:正常对照组和糖尿病组比较差异不显著(P>0.05);微量白蛋白尿组和大量白蛋白尿组明显高于正常白蛋白尿组(24.1%,47.2%,9.4%,P<0.05),大量白蛋白尿组高于微量白蛋白尿组(P<0.05)。②-28C/G的G等位基因型频率:正常对照组和糖尿病组比较差异不显著(P>0.05);微量白蛋白尿组和大量白蛋白尿组明显高于正常白蛋白尿组(12.0%,23.6%,4.7%,P<0.05),大量白蛋白尿组高于微量白蛋白尿组(P<0.05)。③Logistic回归分析表明-28G阳性基因型与糖尿病肾病相关(95%CI为1.402～15.032,P=0.012)。结论:RANTES基因启动子-28G阳性基因型可能与糖尿病肾病相关。

Correlation between polymorphism of regulated upon activation normal T-cell expressed and secreted gene promoter and diabetic nephropathy in type 2 diabetes mellitus

BACKGROUND: Hereditary susceptibility is an important role in episode and development of diabetic nephropathy (DN). Aggregation of monocyte in kidney tissue, differentiation to histocyte and reinforcement of signal are possibly closed to episode and development of DN in type 2 diabetes mellitus (DM). Regulated upon activation normal T-cell expressed and secreted (RANTES) is a chemokine of C-C subtribe. It can mediate infiltration and activation of inflammatory cells and cause injuries of renal corpuscle and renal mesenchymal. This may be a key mechanism of episode and development of DM. Thus, RANTES gene may be one of the susceptible gene of DN. OBJECTIVE :To investigate correlation between RANTES gene promoter -28C/G polymorphism and DN in type 2 DM in Chinese. DESIGN: Case-contrast study. SETTING: Department of Endocrine, Affiliated Hospital of Guiyang Medical College; Center of Diabetes Mellitus of Guizhou Province. PARTICIPANTS: A total of 143 patients with type 2 DM were recruited from the Department of Endocrine, Affiliated Hospital of Guiyang Medical College and Department of Endocrine,Guizhou People's Hospital from September 2003 to September 2005. Among them, 53 cases had normoalbuminuria, 54 microalbuminuria and 36 macroalbuminuria. Another 55 healthy subjects who were selected from Center of Health Examination, Affiliated Hospital of Guiyang Medical College were regarded as control group. METHODS: 3-5 mL peripheral venous blood was collected from all subjects. RANTES gene promoter -28C/G genotype was detected with polymerase chain reaction restriction fragment length polymorphism technique. MAIN OUTCOME MEASURES: ① Allele frequency and genotypic frequency of RANTES gene promoter -28C/G; ② risk factor of DN was analyzed with Logistic regression analysis. RESULTS: All 198 subjects were involved in the final analysis. ① Comparison of CG genotypic frequency of -28C/G: There was no significant difference between normal control group and DM group (P＞ 0.05); however, that in microalbuminuria group and macroalbuminuria group was higher than that in normoalbuminuria group (24.1％, 47.2％, 9.4％, P ＜ 0.05), and that in macroalbuminuria group was also higher than that in microalbuminuria group (P ＜ 0.05). ② Frequency of G allele of -28C/G: There was no significant difference between normal control group and DM group (P ＞ 0.05); however, that in micro albuminuria group and macrealbuminuria group was higher than that in microalbuminuria group (12.0％, 23.6％, 4.7％, P ＜ 0.05), and that in macroalbuminuria group was also higher than that in microalbuminuria group (P＜ 0.05). ③ Logistic regression analysis showed that positive genotype of -28G was related to DN (95％ Cl:1.402-15.032, P =0.012). CONCLUSION: Positive genotype of RANTES gene promoter-28G may be related to DN.