Szczepankiewicz A, Breborowicz A, Sobkowiak P, Kramer L, Popiel A
Department of Pediatric Pulmonology, Allergy and Clinical Immunology, Poznan University of Medical Sciences, Poland.
J Appl Genet. 2009;50(3):275-81. doi: 10.1007/BF03195683.
The aims of this study were: (1) to find associations of asthma with single-nucleotide polymorphisms (SNPs) within the ADRB2 gene: Arg16Gly, Gln27Glu, -1023 G/A, -367 T/C, -47 C/T ; (2) to define linkage disequilibrium in the gene region, basing on the analyzed SNPs; and (3) to analyze the importance of ADRB2 polymorphism for response to bronchodilator drugs in children diagnosed with bronchial asthma. We compared 113 asthmatic children and 123 healthy subjects from the Polish population. Genotyping was performed by PCR-RFLP. We found an association of the A allele of -1023A/G ADRB2 polymorphism with asthma (P = 0.024). No significant associations with other SNPs were detected. Moderate linkage was found between Gln27Glu and -47C/T polymorphisms in linkage disequilibrium analysis (D' = 0.85, r(2) = 0.429, LOD = 31.97). No significant differences were found in haplotype frequencies in comparison to the control group, implicating that they are not associated with susceptibility to asthma in the analyzed population. There was no significant correlation between the analyzed SNPs of the ADRB2 gene and the response to beta(2)-agonists. This is the first report providing suggestive evidence for association of -1023A/G ADRB2 polymorphism with an increased risk of asthma. The analyzed SNPs may not play a major role in response to beta(2)-agonists in asthmatic children.
（1）寻找哮喘与ADRB2基因内单核苷酸多态性（SNP）的关联：Arg16Gly、Gln27Glu、-1023 G/A、-367 T/C、-47 C/T；（2）基于分析的SNP确定基因区域的连锁不平衡；（3）分析ADRB2基因多态性对诊断为支气管哮喘儿童支气管扩张剂药物反应的重要性。我们比较了来自波兰人群的113名哮喘儿童和123名健康受试者。通过PCR-RFLP进行基因分型。我们发现-1023A/G ADRB2多态性的A等位基因与哮喘有关联（P = 0.024）。未检测到与其他SNP的显著关联。在连锁不平衡分析中发现Gln27Glu和-47C/T多态性之间存在中度连锁（D' = 0.85，r(2) = 0.429，LOD = 31.97）。与对照组相比，单倍型频率未发现显著差异，这表明它们与分析人群中的哮喘易感性无关。ADRB2基因的分析SNP与β2激动剂的反应之间没有显著相关性。这是第一份提供-1023A/G ADRB2多态性与哮喘风险增加相关的提示性证据的报告。分析的SNP可能在哮喘儿童对β2激动剂的反应中不发挥主要作用。
