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肥胖发病年龄、转录因子7样2(TCF7L2)rs7903146多态性、脂联素水平与肥胖患者2型糖尿病风险

Age at onset of obesity, transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism, adiponectin levels and the risk of type 2 diabetes in obese patients.

作者信息

Wrzosek Małgorzata, Sawicka Ada, Wrzosek Michał, Piątkiewicz Paweł, Tałałaj Marek, Nowicka Grażyna

机构信息

Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy and Center for Preclinical Studies, Medical University of Warsaw, Warsaw, Poland.

Department of Geriatrics, Internal Medicine and Metabolic Bone Diseases, Medical Centre of Postgraduate Education, Orlowski Hospital, Warsaw, Poland.

出版信息

Arch Med Sci. 2019 Mar;15(2):321-329. doi: 10.5114/aoms.2017.69638. Epub 2017 Nov 17.

Abstract

INTRODUCTION

Interaction between obesity and genetic factors involved in the regulatory pathways of glucose homeostasis may play a significant role in diabetes development in the obese. The aim of this study was to investigate the associations between the TCF7L2 rs7903146 polymorphism, adiponectin levels, age at onset of obesity and the occurrence of type 2 diabetes (T2D) in a sample of obese Polish adults.

MATERIAL AND METHODS

A total of 474 unrelated obese subjects were included in this study. Real-time PCR was used to detect the TCF7L2 rs7903146 polymorphism. Serum level of adiponectin was determined by the ELISA method. Standard assays were used to measure total cholesterol, HDL cholesterol, triglycerides, glucose and HbA concentrations. We used multiple logistic regression to identify factors associated with type 2 diabetes.

RESULTS

We found that the T allele of rs7903146 was significantly associated with T2D risk (odds ratio of 1.59 for T allele, = 0.005). This association persisted after adjusting for confounders in the recessive model (odds ratio of 3.54 for TT genotype, = 0.011). Serum adiponectin levels were significantly lower in diabetic subjects than in nondiabetic individuals (3.6 vs. 5.6 µg/ml, < 0.001). Participants who were obese at age ≥ 20 years had significantly higher odds of having T2D (OR = 4.94) than those with the onset of obesity before 20 years ( < 0.001).

CONCLUSIONS

Our study highlights the significance of the relationship between the TCF7L2 polymorphism, a person's age at onset of obesity and the prevalence of T2D, and confirms lower adiponectin levels in obese diabetics in comparison to obese nondiabetics.

摘要

引言

肥胖与参与葡萄糖稳态调节途径的遗传因素之间的相互作用可能在肥胖人群患糖尿病的过程中起重要作用。本研究旨在调查波兰肥胖成年人样本中,转录因子7样蛋白2(TCF7L2)基因rs7903146多态性、脂联素水平、肥胖发病年龄与2型糖尿病(T2D)发生之间的关联。

材料与方法

本研究共纳入474名无亲缘关系的肥胖受试者。采用实时聚合酶链反应(PCR)检测TCF7L2基因rs7903146多态性。采用酶联免疫吸附测定(ELISA)法测定血清脂联素水平。使用标准检测方法测量总胆固醇、高密度脂蛋白胆固醇、甘油三酯、血糖和糖化血红蛋白(HbA)浓度。我们使用多元逻辑回归分析来确定与2型糖尿病相关的因素。

结果

我们发现rs7903146的T等位基因与T2D风险显著相关(T等位基因的比值比为1.59,P = 0.005)。在隐性模型中对混杂因素进行校正后,这种关联仍然存在(TT基因型的比值比为3.54,P = 0.011)。糖尿病患者的血清脂联素水平显著低于非糖尿病个体(3.6对5.6μg/ml,P < 0.001)。20岁及以上肥胖的参与者患T2D的几率(OR = 4.94)显著高于20岁之前开始肥胖的参与者(P < 0.001)。

结论

我们的研究强调了TCF7L2基因多态性、个体肥胖发病年龄与T2D患病率之间关系的重要性,并证实肥胖糖尿病患者的脂联素水平低于肥胖非糖尿病患者。

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