血液和内脏脂肪组织中 ADRB3 基因启动子 DNA 甲基化与男性代谢紊乱有关。

ADRB3 gene promoter DNA methylation in blood and visceral adipose tissue is associated with metabolic disturbances in men.

机构信息

Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada.

出版信息

Epigenomics. 2014 Feb;6(1):33-43. doi: 10.2217/epi.13.82.

DOI:10.2217/epi.13.82

PMID:24579945

Abstract

AIM

ADRB3 DNA hypermethylation was recently associated with dyslipidemia in familial hypercholesterolemia (FH). In this study, we verified whether ADRB3 DNA methylation in blood and visceral adipose tissue (VAT) was associated with obesity and its related complications.

METHODS

DNA methylation levels were measured in the blood of 61 FH men, and the blood and VAT of 30 severely obese men. Common ADRB3 polymorphisms were genotyped in all subjects.

RESULTS

Higher ADRB3 DNA methylation levels were significantly associated with lower low-density lipoprotein cholesterol levels (r = -0.40; p = 0.01) in FH, and with a lower waist-to-hip ratio (r = -0.55; p = 0.01) and higher blood pressure (r = 0.43; p = 0.05) in severely obese men. ADRB3 g.-843C>T and p.W64R polymorphisms were found to be strongly associated (p < 0.001) with ADRB3 DNA methylation and mRNA levels.

CONCLUSION

Although further studies are needed, these results suggest that epigenetic changes at the ADRB3 gene locus might be involved in the development of obesity and its related metabolic complications.

摘要

目的

最近有研究表明，ADRB3 基因 DNA 超甲基化与家族性高胆固醇血症（FH）患者的血脂异常有关。本研究旨在验证血液和内脏脂肪组织（VAT）中 ADRB3 基因 DNA 甲基化与肥胖及其相关并发症之间的关系。

方法

对 61 名 FH 男性的血液和 30 名重度肥胖男性的血液和 VAT 进行 DNA 甲基化水平检测。所有受试者均进行常见 ADRB3 多态性基因分型。

结果

在 FH 患者中，ADRB3 基因 DNA 甲基化水平与低密度脂蛋白胆固醇水平呈负相关（r = -0.40；p = 0.01），与腰围臀围比（r = -0.55；p = 0.01）和血压（r = 0.43；p = 0.05）呈负相关。ADRB3 g.-843C>T 和 p.W64R 多态性与 ADRB3 基因 DNA 甲基化和 mRNA 水平呈强相关（p < 0.001）。