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印度南部人群中热休克蛋白-70基因A1538G和C2437T单核苷酸多态性与糖尿病肾病的关联

Association of A1538G and C2437T single nucleotide polymorphisms in heat shock protein-70 genes with diabetic nephropathy among South Indian population.

作者信息

Dhamodharan Umapathy, Ezhilarasi Krishnamoorthy, Ponjayanthi Balashanmugam, Sireesh Dornadula, Ramkumar Kunka Mohanram, Viswanathan Vijay

机构信息

Life Science Division, SRM Research Institute, SRM University, Kattankulathur, Chennai-603203, India.

Department of Biochemistry and Molecular Genetics, Prof. M. Viswanathan Diabetes Research Centre and M.V. Hospital for Diabetes (A WHO Collaborating Centre for Research, Education & Training in Diabetes), Royapuram, Chennai-600013, India.

出版信息

Biosci Rep. 2017 Mar 27;37(2). doi: 10.1042/BSR20160605. Print 2017 Apr 28.

Abstract

Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease, characterized by progressive albuminuria and conferring additional risk of cardiovascular disease (CVD) and mortality. The crucial role of heat-shock proteins (HSPs) on renal function in patients with DN has been well documented. The present study was aimed to understand the association of gene variants on the susceptibility of Type 2 Diabetes Mellitus (T2DM) and DN. A total of 946 subjects (549 Males; 397 Females) were recruited and divided into four groups according to the levels of urinary albumin excretion (UAE): those with normoalbuminuria (UAE <30 mg/24 h; =230), those with microalbuminuria (30≤ UAE ≤300 mg/24 h; =230), and those with macroalbuminuria (UAE> 300 mg/24 h; =230). The control group randomly enrolled a consecutive population of 256 healthy subjects who had a routine medical check-up in our hospital. Those subjects had no history or clinical symptoms of diabetes. Subjects were genotyped for (+1538 A/G; rs2763979) and (+2437 C/T; rs2227956) by PCR-restriction fragment length polymorphism (RFLP). The 'G' allele of (+1538 A/G) single nucleotide polymorphism (SNP) showed relative risk for normoalbuminuria, microalbuminuria and macroalbuminuria subjects whereas the 'T' allele of (+2437 C/T) SNP showed significant protection against macroalbuminuria subjects. In conclusion, our results indicate that the (+1538 A/G) and (+2437 C/T) SNPs are highly associated with renal complications in T2DM among the South Indian population.

摘要

糖尿病肾病(DN)是终末期肾病的主要病因,其特征为进行性蛋白尿,并伴有心血管疾病(CVD)和死亡的额外风险。热休克蛋白(HSPs)在DN患者肾功能中的关键作用已有充分记录。本研究旨在了解基因变异与2型糖尿病(T2DM)及DN易感性之间的关联。共招募了946名受试者(549名男性;397名女性),并根据尿白蛋白排泄(UAE)水平分为四组:正常白蛋白尿组(UAE<30mg/24h;=230)、微量白蛋白尿组(30≤UAE≤300mg/24h;=230)和大量白蛋白尿组(UAE>300mg/24h;=230)。对照组随机纳入了在我院进行常规体检的256名健康受试者。这些受试者无糖尿病病史或临床症状。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对受试者进行(+1538A/G;rs2763979)和(+2437C/T;rs2227956)基因分型。(+1538A/G)单核苷酸多态性(SNP)的“G”等位基因显示出对正常白蛋白尿、微量白蛋白尿和大量白蛋白尿受试者的相对风险,而(+2437C/T)SNP的“T”等位基因对大量白蛋白尿受试者显示出显著的保护作用。总之,我们的结果表明,在南印度人群中,(+1538A/G)和(+2437C/T)SNP与T2DM的肾脏并发症高度相关。

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