ADRB3基因rs4994位点在冠状动脉疾病发展过程中的重要作用。

Significant role of ADRB3 rs4994 towards the development of coronary artery disease.

作者信息

Kumar Surendra, Mishra Avshesh, Srivastava Anshika, Mittal Tulika, Garg Naveen, Mittal Balraj

机构信息

Departments of aGenetics bCardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India.

出版信息

Coron Artery Dis. 2014 Jan;25(1):29-34. doi: 10.1097/MCA.0000000000000056.

DOI:10.1097/MCA.0000000000000056

PMID:24201118

Abstract

BACKGROUND

Coronary artery disease (CAD) is the most common type of heart disease and cause of heart attacks. It has been proposed that both the susceptibility to disease and the interindividual variability in response to treatment relates in part to genetic polymorphisms, particularly those polymorphisms for neurotransmitter and drug receptors. Common functional polymorphisms in β-adrenergic receptor genes (ADRB) have been associated with heart failure phenotypes. Therefore, the purpose of the present study was to explore the association of genetic variants in ADRB3 (C190T or Trp64Arg) ADRB1 (C1165G or Arg389Gly), and ADRA2A (C-1291G) with CAD.

MATERIALS AND METHODS

The present study recruited a total of 600 consecutive patients with angiographically confirmed CAD and 200 population-matched controls (173 men and 27 women) (mean age 54.10±8.30 years). The ADRB3 T190C, ADRA2A C-1291G, and ADRB1 C1165G polymorphisms were determined by PCR-restriction fragment length polymorphism. The putative functional effects were determined in the coding region of the ADRD3 gene by online web servers FASTSNP and F-SNP.

RESULTS

On comparing the genotype frequency distribution in CAD patients with that of healthy individuals, significant association was observed with the CC genotype of the ADRB3 T190C polymorphism (P=0.040, odds ratio=1.5). Also, at the allelic level the C allele of ADRB3 T190C conferred risk for CAD (P=0.005, odds ratio=1.7). The ADRA2A C-1291G and ADRB1 C1165G polymorphisms were not found to be a risk for CAD when compared with controls.

CONCLUSION

The present study finding suggests that ADRB3 C190T may also be involved in the complex pathophysiology of CAD.

摘要

背景

冠状动脉疾病（CAD）是最常见的心脏病类型及心脏病发作的病因。有人提出，疾病易感性和个体对治疗反应的个体差异部分与基因多态性有关，特别是那些神经递质和药物受体的多态性。β-肾上腺素能受体基因（ADRB）中的常见功能多态性与心力衰竭表型相关。因此，本研究的目的是探讨ADRB3（C190T或Trp64Arg）、ADRB1（C1165G或Arg389Gly）和ADRA2A（C-1291G）基因变异与CAD的关联。

材料与方法

本研究共招募了600例经血管造影确诊的CAD连续患者和200例人群匹配对照（173名男性和27名女性）（平均年龄54.10±8.30岁）。通过聚合酶链反应-限制性片段长度多态性测定ADRB3 T190C、ADRA2A C-1291G和ADRB1 C1165G多态性。通过在线网络服务器FASTSNP和F-SNP在ADRD3基因的编码区确定推定的功能效应。

结果

将CAD患者的基因型频率分布与健康个体进行比较时，观察到ADRB3 T190C多态性的CC基因型存在显著关联（P = 0.040，比值比 = 1.5）。此外，在等位基因水平上，ADRB3 T190C的C等位基因赋予CAD风险（P = 0.005，比值比 = 1.7）。与对照组相比，未发现ADRA2A C-1291G和ADRB1 C1165G多态性是CAD的风险因素。