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β2肾上腺素能受体基因多态性与哮喘关联的系统评价和荟萃分析:一项HuGE评价

Systematic review and meta-analysis of the association between {beta}2-adrenoceptor polymorphisms and asthma: a HuGE review.

作者信息

Thakkinstian Ammarin, McEvoy Mark, Minelli Cosetta, Gibson Peter, Hancox Bob, Duffy David, Thompson John, Hall Ian, Kaufman Joel, Leung Ting-Fan, Helms Peter Joseph, Hakonarson Hakon, Halpi Eva, Navon Ruth, Attia John

机构信息

Clinical Epidemiology Unit, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Am J Epidemiol. 2005 Aug 1;162(3):201-11. doi: 10.1093/aje/kwi184. Epub 2005 Jun 29.

Abstract

A number of studies have investigated two common polymorphisms in the beta(2)-adrenoceptor gene, Arg/Gly16 and Gln/Glu27, in relation to asthma susceptibility. The authors performed a meta-analysis of each polymorphism, as well as haplotype analysis, for adult and pediatric populations separately, using published data, supplemented by additional data requested from the original authors. Individual analysis detected no effect of Arg/Gly16 in adults but did suggest a recessive protective effect of Gly16 for children, with an odds ratio of 0.71 (95% confidence interval (CI): 0.53, 0.96) compared with the other genotypes. Results for Gln/Glu27 in adults seem to indicate that heterozygotes are at decreased risk of asthma than either homozygote (odds ratio = 0.73, 95% CI: 0.62, 0.87), although the studies are heterogeneous; in children, the Glu/Glu genotype has a decreased risk of asthma (odds ratio = 0.60, 95% CI: 0.35, 0.99) compared with the other genotypes. Despite the proximity of these two polymorphic sites, the linkage disequilibrium coefficient of 0.41 was not high (p < 0.001). Haplotype analysis suggests that there may be an interaction between the two sites, with a lower risk of asthma associated with the Glu27 allele (compared with Gln27), and that this risk is modified by the allele at position 16.

摘要

多项研究调查了β₂肾上腺素能受体基因中的两种常见多态性,即Arg/Gly16和Gln/Glu27,与哮喘易感性的关系。作者分别对成人和儿童人群的每种多态性进行了荟萃分析以及单倍型分析,使用已发表的数据,并补充了向原始作者索要的额外数据。个体分析未发现Arg/Gly16对成人有影响,但确实表明Gly16对儿童有隐性保护作用,与其他基因型相比,优势比为0.71(95%置信区间(CI):0.53,0.96)。成人中Gln/Glu27的结果似乎表明,杂合子患哮喘的风险低于任何一种纯合子(优势比 = 0.73,95% CI:0.62,0.87),尽管研究存在异质性;在儿童中,与其他基因型相比,Glu/Glu基因型患哮喘的风险降低(优势比 = 0.60,95% CI:0.35,0.99)。尽管这两个多态性位点相邻,但连锁不平衡系数0.41并不高(p < 0.001)。单倍型分析表明,这两个位点之间可能存在相互作用,Glu27等位基因(与Gln27相比)与较低的哮喘风险相关,并且该风险会因第16位的等位基因而改变。

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