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溶质载体家族2成员4基因(SLC2A4)5'-非翻译区的单核苷酸多态性调节内脏脂肪组织中溶质载体家族2成员4基因的表达。

Single nucleotide polymorphisms in 5'-UTR of the SLC2A4 gene regulate solute carrier family 2 member 4 gene expression in visceral adipose tissue.

作者信息

Malodobra-Mazur Malgorzata, Bednarska-Chabowska Dorota, Olewinski Robert, Chmielecki Zygmunt, Adamiec Rajmund, Dobosz Tadeusz

机构信息

Department of Forensic Medicine, Molecular Techniques Unit, Wroclaw Medical University, Sklodowskiej-Curie 52, 50-369 Wroclaw, Poland.

Department of Angiology, Hypertension and Diabetology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.

出版信息

Gene. 2016 Jan 15;576(1 Pt 3):499-504. doi: 10.1016/j.gene.2015.10.067. Epub 2015 Oct 31.

Abstract

BACKGROUND

The glucose uptake by numerous cells like adipocytes or skeletal muscle cells requires activation of specific proteins called glucose transporters. GLUT4 content and its activation as well as SLC2A4 gene expression level are decreased in patients with type 2 diabetes. The SLC2A4 gene expression rate might be modulated by genetic variances in UTRs. The relationship between two SNPs in 5'UTR and one SNP in 3'UTR and SLC2A4 gene expression rate in adipose tissue and lymphocytes has been evaluated.

METHODS

The study was performed on lymphocytes collected from 34 type 2 diabetic patients and equal number of controls. Visceral adipose tissue biopsies were collected from 15 patients with T2DM and from 24 controls.

RESULTS

SLC2A4 gene expression level was slightly lower within type 2 diabetic patients in both type of tissues. Furthermore, the negative correlation between SLC2A4 gene expression level in visceral adipose tissue and BMI has been noticed. The genotypes of two SNPs in 5'UTRs (rs5417 and rs5418) were correlated with lower mRNA amount of GLUT4 within recessive homozygotes belonging to control group.

CONCLUSIONS

Present results suggest the relationship between genetic variances within UTRs of SLC2A4 gene and gene expression rate. However, the relationship is tissue specific and is noticeable in adipose tissue of lean and healthy subjects.

摘要

背景

许多细胞如脂肪细胞或骨骼肌细胞摄取葡萄糖需要激活特定的蛋白质,即葡萄糖转运体。2型糖尿病患者的葡萄糖转运蛋白4(GLUT4)含量及其活性以及溶质载体家族2成员4(SLC2A4)基因表达水平均降低。SLC2A4基因的表达率可能受非翻译区(UTR)基因变异的调节。本研究评估了5'UTR中的两个单核苷酸多态性(SNP)和3'UTR中的一个SNP与脂肪组织和淋巴细胞中SLC2A4基因表达率之间的关系。

方法

本研究对34例2型糖尿病患者和数量相等的对照者采集的淋巴细胞进行检测。对15例2型糖尿病患者和24例对照者进行内脏脂肪组织活检。

结果

在两种组织中,2型糖尿病患者的SLC2A4基因表达水平均略低。此外,还发现内脏脂肪组织中SLC2A4基因表达水平与体重指数(BMI)呈负相关。5'UTR中两个SNP(rs5417和rs5418)的基因型与对照组隐性纯合子中较低的GLUT4 mRNA量相关。

结论

目前的研究结果表明SLC2A4基因UTR内的基因变异与基因表达率之间存在关联。然而,这种关联具有组织特异性,在瘦的健康受试者的脂肪组织中较为明显。

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