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2型糖尿病易感基因座与中国糖尿病患者外周神经功能的关联

Association of type 2 diabetes susceptibility loci with peripheral nerve function in a Chinese population with diabetes.

作者信息

Lu Jingyi, Luo Yi, Wang Jie, Hu Cheng, Zhang Rong, Wang Congrong, Jia Weiping

机构信息

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Shanghai Diabetes Institute, Shanghai, China.

出版信息

J Diabetes Investig. 2017 Jan;8(1):115-120. doi: 10.1111/jdi.12546. Epub 2016 Jul 9.

Abstract

AIMS/INTRODUCTION: Previous studies have suggested a possible relationship between type 2 diabetes mellitus susceptibility loci and diabetic complications. The present study aimed to investigate the associations between type 2 diabetes mellitus loci with peripheral nerve function in a Chinese population with type 2 diabetes mellitus.

MATERIALS AND METHODS

A total of 1,900 type 2 diabetes mellitus patients were recruited in the study. We selected ten single nucleotide polymorphisms (SNPs) from ten type 2 diabetes mellitus susceptibility genes previously confirmed in Chinese patients. Genotyping was carried out by using a MassARRAY Compact Analyzer. Peripheral nerve function was evaluated by nerve conduction studies in all participants. The composite Z-scores for nerve conduction parameters including conduction velocity (CV), amplitude and latency were calculated, respectively.

RESULTS

Rs5219 of KCNJ11 (E23K, G→A) was identified to be associated with all the parameters obtained from nerve conduction studies (Z-score of CV: β = 0.113, P = 0.01; Z-score of amplitude: β = 0.133, P = 0.01; Z-score of latency: β = -0.116, P = 0.01) after adjustment for covariates including age, duration and glycated hemoglobin. Specifically, each copy of the A allele was related to better outcomes. CDKAL1 rs7756992 and TCF7L2 rs7903146 correlated with the composite Z-score of amplitude (P = 0.028 and P = 0.016, respectively), but not CV (P = 0.393 and P = 0.281, respectively) or latency (P = 0.286 and P = 0.273, respectively). There were no significant associations between the other seven SNPs and peripheral nerve function.

CONCLUSIONS

Rs5219 at KCNJ11 (E23K) was associated with peripheral nerve function in a Chinese population with type 2 diabetes mellitus, suggesting shared genetic factors for type 2 diabetes mellitus and diabetic polyneuropathy in this population.

摘要

目的/引言:既往研究提示2型糖尿病易感基因座与糖尿病并发症之间可能存在关联。本研究旨在调查中国2型糖尿病患者群体中2型糖尿病基因座与外周神经功能之间的关联。

材料与方法

本研究共纳入1900例2型糖尿病患者。我们从先前在中国患者中已得到证实的10个2型糖尿病易感基因中选取了10个单核苷酸多态性(SNP)。采用MassARRAY Compact Analyzer进行基因分型。对所有参与者进行神经传导研究以评估外周神经功能。分别计算包括传导速度(CV)、波幅和潜伏期在内的神经传导参数的综合Z值。

结果

在校正年龄、病程和糖化血红蛋白等协变量后,发现KCNJ11基因的Rs5219(E23K,G→A)与神经传导研究获得的所有参数均相关(CV的Z值:β = 0.113,P = 0.01;波幅的Z值:β = 0.133,P = 0.01;潜伏期的Z值:β = -0.116,P = 0.01)。具体而言,A等位基因的每个拷贝均与更好的结果相关。CDKAL1基因的rs7756992和TCF7L2基因的rs7903146与波幅的综合Z值相关(P分别为0.028和0.016),但与CV(P分别为0.393和0.281)或潜伏期(P分别为0.286和0.273)无关。其他7个SNP与外周神经功能之间无显著关联。

结论

KCNJ11基因的Rs5219(E23K)与中国2型糖尿病患者群体的外周神经功能相关,提示该群体中2型糖尿病和糖尿病性多发性神经病存在共同的遗传因素。

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