Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, West Perth, Western Australia, Australia.
Respirology. 2011 Feb;16(2):359-66. doi: 10.1111/j.1440-1843.2010.01917.x.
Haplotypes in the promoter region of the prostanoid DP receptor (PTGDR) gene have been shown to functionally influence gene transcription and to be associated with asthma in two previous case-control studies in Caucasians. This study tested the association of PTGDR haplotypes with asthma phenotypes in two large Caucasian-Australian populations. These results were incorporated in a meta-analysis with previously published data to determine the overall role for these haplotypes in the risk of asthma.
Three PTGDR promoter-region single nucleotide polymorphisms (SNP) were genotyped in 368 individuals from the Western Australian Twin Child Health study and 2988 individuals from the Busselton Health Study. Logistic regression and transition disequilibrium tests were used to assess whether SNP genotypes and three SNP haplotypes were associated with doctor-diagnosed asthma or intermediate quantitative traits. Longitudinal data from the Busselton Health Study were used to examine whether PTGDR influences changes in lung function over time. Meta-analysis incorporated the findings of this study with those of two previous studies in Caucasian populations.
Cross-sectional associations between PTGDR haplotypes and asthma phenotypes were non-significant (P > 0.05) in both populations. Longitudinal analyses of PTGDR and lung function were also non-significant. Meta-analysis, however, suggested that haplotype TCT was significantly associated with decreased risk of asthma (OR = 0.76; P = 0.02) while haplotype CCC was not significantly associated with asthma (OR = 1.30; P = 0.07).
These results suggest that despite the non-significant findings in the present study populations, PTGDR promoter haplotypes may account for a small but significant proportion of the risk of asthma in Caucasian populations.
先前的两项在白种人人群中进行的病例对照研究表明，前列腺素 DP 受体（PTGDR）基因启动子区域的单倍型与基因转录的功能有关，并与哮喘有关。本研究在两个大型的白种人澳大利亚人群中检测了 PTGDR 单倍型与哮喘表型的关联。这些结果与先前发表的数据一起进行荟萃分析，以确定这些单倍型在哮喘风险中的总体作用。
在西澳大利亚双胞胎儿童健康研究中的 368 名个体和在巴瑟尔顿健康研究中的 2988 名个体中，对三个 PTGDR 启动子区域单核苷酸多态性（SNP）进行了基因分型。逻辑回归和转换不平衡检验用于评估 SNP 基因型和三个 SNP 单倍型是否与医生诊断的哮喘或中间定量性状有关。巴瑟尔顿健康研究的纵向数据用于检查 PTGDR 是否影响随时间推移的肺功能变化。荟萃分析将本研究的结果与两个先前在白种人群中进行的研究的结果结合在一起。
在两个人群中，PTGDR 单倍型与哮喘表型之间的横断面关联均无统计学意义（P > 0.05）。PTGDR 和肺功能的纵向分析也无统计学意义。然而，荟萃分析表明，TCT 单倍型与哮喘风险降低显著相关（OR = 0.76；P = 0.02），而 CCC 单倍型与哮喘无显著相关性（OR = 1.30；P = 0.07）。
尽管本研究人群中未发现有统计学意义的结果，但 PTGDR 启动子单倍型可能在白种人群的哮喘风险中占很小但有统计学意义的一部分。
