通过多重聚合酶链反应分析测定β2-肾上腺素能受体（ADRB2）单倍型。

Determination of beta2-adrenergic receptor (ADRB2) haplotypes by a multiplexed polymerase chain reaction assay.

作者信息

Littlejohn Mathew D, Taylor D Robin, Miller Allison L, Kennedy Martin A

机构信息

Gene Structure and Function Laboratory, Department of Pathology, Christchurch School of Medicine and Health Sciences, University of Otago, P.O. Box 4345, Christchurch, New Zealand.

出版信息

Hum Mutat. 2002 Dec;20(6):479. doi: 10.1002/humu.9091.

DOI:10.1002/humu.9091

PMID:12442282

Abstract

The beta2-adrenergic receptor (B2AR or ADRB2) is the target of beta2-agonist drugs used for bronchodilation in asthma and other respiratory diseases. The gene for this receptor (ADRB2) contains numerous single nucleotide polymorphisms (SNPs) some of which may be of pharmacogenetic relevance, although a consistent picture of genotype-phenotype relationships has yet to emerge. Recently, 12 distinct haplotypes of ADRB2were described along with preliminary evidence that certain haplotypes, rather than specific SNPs, determine differential response to the beta-agonist drug albuterol. In order to further evaluate the role of ADRB2haplotypes as pharmacogenetic determinants, simple and accurate methods for haplotyping clinical samples are required. To this end we have developed a multiplexed, allele-specific PCR assay that interrogates six ADRB2 SNPs in a manner that permits rapid and accurate assignment of ADRB2 haplotype pairs. This assay will facilitate studies of ADRB2haplotypes in phenotypes such as patient responses to beta2-agonists, bronchial hyper-responsiveness, and cardiovascular conditions.

摘要

β2肾上腺素能受体（B2AR或ADRB2）是用于哮喘和其他呼吸系统疾病支气管扩张的β2激动剂药物的靶点。该受体的基因（ADRB2）包含众多单核苷酸多态性（SNP），其中一些可能具有药物遗传学相关性，尽管基因型-表型关系的一致图景尚未出现。最近，描述了ADRB2的12种不同单倍型，并有初步证据表明某些单倍型而非特定SNP决定了对β激动剂药物沙丁胺醇的不同反应。为了进一步评估ADRB2单倍型作为药物遗传学决定因素的作用，需要用于临床样本单倍型分型的简单准确方法。为此，我们开发了一种多重等位基因特异性PCR检测方法，该方法以允许快速准确确定ADRB2单倍型对的方式检测六个ADRB2 SNP。该检测方法将有助于在诸如患者对β2激动剂的反应、支气管高反应性和心血管疾病等表型中研究ADRB2单倍型。