Al-Abdulhadi S A, Helms P J, Main M, Smith O, Christie G
Department of Child Health, University of Aberdeen, Royal Aberdeen Children Hospital, Aberdeen AB25 2ZG, Scotland, UK.
Genes Immun. 2005 Feb;6(1):24-30. doi: 10.1038/sj.gene.6364151.
Asthma is a complex inherited disease. The study was undertaken to identify the association of RANTES promoter polymorphisms with atopy and asthma using family-based association tests (FBATs) and generation-specific case-control analyses. We identified 154 nuclear families (453 individuals) in whom we established RANTES promoter status using the RFLP-PCR method. Of the two known promoter polymorphisms -403G/A and -28C/G, only the former appeared with a clinically relevant frequency. A total of 61 families were eligible for assessment of transmission of the allele with asthma and atopy by the pedigree disequilibrium test (PDT). Overall, allele frequency for -403A was 38.3% and 84 of 89 (94.3%) alleles were transmitted with physician diagnosed asthma (PDA) (P=0.001). All 89 children with atopy received the mutant allele, which was more than expected following Mendelian Laws of transmission (P=0.0001). In 303 unrelated parents, significant associations of the mutant allele were for atopy with or without asthma (P=0.001). In 150 unrelated children, significant associations were for atopy alone (P=0.001) and asthma (P=0.001). No associations were found for bronchial hyper-responsiveness (BHR). The -403 G --> A is transmitted with atopy and atopic asthma, although its contribution appears to relate more to atopy than asthma and BHR.
哮喘是一种复杂的遗传性疾病。本研究旨在通过基于家系的关联检验(FBATs)和特定代际的病例对照分析,确定RANTES启动子多态性与特应性和哮喘之间的关联。我们识别出154个核心家庭(453名个体),并使用RFLP-PCR方法确定了RANTES启动子状态。在两种已知的启动子多态性-403G/A和-28C/G中,只有前者以临床相关频率出现。共有61个家庭符合通过系谱不平衡检验(PDT)评估哮喘和特应性等位基因传递的条件。总体而言,-403A的等位基因频率为38.3%,89个等位基因中有84个(94.3%)与医生诊断的哮喘(PDA)一起传递(P=0.001)。所有89名患有特应性的儿童都获得了突变等位基因,这超过了孟德尔遗传定律预期的传递频率(P=0.0001)。在303名无亲缘关系的父母中,突变等位基因与伴有或不伴有哮喘的特应性有显著关联(P=0.001)。在150名无亲缘关系的儿童中,显著关联分别为单独的特应性(P=0.001)和哮喘(P=0.001)。未发现与支气管高反应性(BHR)有关联。-403 G→A与特应性和特应性哮喘一起传递,尽管其作用似乎更多地与特应性而非哮喘和BHR相关。