Zhu G, Vestbo J, Lenney W, Silverman M, Whyte M, Helms P, Anderson W H, Pillai S G
Medical Genetics, Glaxo SmithKline, Research Triangle Park, NC 27709, USA.
Genes Immun. 2007 Jul;8(5):398-403. doi: 10.1038/sj.gene.6364399. Epub 2007 May 31.
The prostanoid DP receptor (PTGDR) is shown to be involved in the asthma patho-physiology and the results from the published genetic association studies are inconsistent. Four single nucleotide polymorphisms (SNPs) in PTGDR were genotyped in 342 and 294 families from UK and Denmark respectively. Asthma and asthma-related phenotypes were analyzed using family-based association analyses. In the UK families, a promoter polymorphism (-731A/G) showed significant associations with asthma (P=0.0022), atopic asthma (P=0.0044), bronchial hyperreactivity or BHR (P=0.00120) and strict asthma (P=0.0008). The P-values for asthma, BHR and strict asthma were significant even after the most stringent correction for the number of markers and the number of phenotypes analyzed (<0.0031). An intronic polymorphism (+6651C/T) also showed significant associations with asthma (P=0.0302), atopic asthma (P=0.0131), BHR (P=0.0249) and strict asthma (P=0.0261). In the Danish families, an intronic polymorphism (+6541C/T) showed significant associations with asthma (P=0.0071), atopic asthma (P=0.0348), BHR (P=0.0033) and strict asthma (P=0.0381). The results of haplotype analyses supported the ones of the single SNP analyses. Thus, we demonstrated significant evidence of association between polymorphisms in PTGDR with asthma phenotypes in the two Caucasian populations.
前列腺素DP受体(PTGDR)被证明与哮喘病理生理学有关,而已发表的基因关联研究结果并不一致。分别在来自英国和丹麦的342个及294个家庭中对PTGDR中的四个单核苷酸多态性(SNP)进行了基因分型。使用基于家系的关联分析方法对哮喘及与哮喘相关的表型进行了分析。在英国家庭中,一个启动子多态性(-731A/G)与哮喘(P=0.0022)、特应性哮喘(P=0.0044)、支气管高反应性(BHR,P=0.00120)及重症哮喘(P=0.0008)显示出显著关联。即使在对所分析的标记数量和表型数量进行最严格校正后,哮喘、BHR及重症哮喘的P值仍具有显著性(<0.0031)。一个内含子多态性(+6651C/T)也与哮喘(P=0.0302)、特应性哮喘(P=0.0131)、BHR(P=0.0249)及重症哮喘(P=0.0261)显示出显著关联。在丹麦家庭中,一个内含子多态性(+6541C/T)与哮喘(P=0.0071)、特应性哮喘(P=0.0348)、BHR(P=0.0033)及重症哮喘(P=0.0381)显示出显著关联。单倍型分析结果支持了单个SNP分析的结果。因此,我们证明了在这两个白种人群体中PTGDR多态性与哮喘表型之间存在显著的关联证据。