Sanz C, Isidoro-García M, Dávila I, Moreno E, Laffond E, Avila C, Lorente F
Department of Allergy, University Hospital of Salamanca, Salamanca, Spain.
Allergy. 2006 May;61(5):543-8. doi: 10.1111/j.1398-9995.2006.01025.x.
PTGDR gene has been identified as an asthma-susceptibility gene. Recently, functional genetic variants have been associated with asthma. The objective of this work was to study -549T>C, -441C>T and -197T>C PTGDR promoter polymorphisms in a Spanish population.
In this study, 197 Caucasian individuals were included. Asthma was specialist-physician diagnosed according to the American Thoracic Society (ATS) criteria and classified following the Global Initiative for Asthma (GINA) guidelines. Skin prick tests were performed in all patients. The polymorphisms were analyzed by direct sequencing.
-197T>C polymorphism was significantly associated with asthma [Fisher's P-value = 0.007, Monte Carlo P-value (10(4) simulations) = 0.004]. Multivariate analysis adjusted for age and sex confirmed this association with an increased risk of asthma (OR, 3.06; 95% CI, 1.28-7.32; P-value = 0.012). CCT CCC diplotype was associated with asthma (P-value < 0.0001; OR, 1.15; 95% CI, 1.07-1.23), specifically with allergic asthma (P-value < 0.0001). CCT CCC diplotype is unambiguous. All individuals carrying this diplotype had asthma.
We identified a specific promoter variant of PTGDR that could be associated with asthma. This diplotype is a combination of the two highest transcriptional efficiency haplotypes, recently described. Our in vivo results would support for the first time what was demonstrated in vitro about high-transcriptional efficiency PTGDR haplotypes in asthma.
PTGDR基因已被确定为哮喘易感基因。最近，功能性基因变异与哮喘有关。这项研究的目的是研究西班牙人群中PTGDR启动子的-549T>C、-441C>T和-197T>C多态性。
本研究纳入了197名白种人个体。根据美国胸科学会（ATS）标准由专科医生诊断哮喘，并按照全球哮喘防治创议（GINA）指南进行分类。对所有患者进行皮肤点刺试验。通过直接测序分析多态性。
-197T>C多态性与哮喘显著相关[费舍尔P值=0.007，蒙特卡洛P值（10⁴次模拟）=0.004]。对年龄和性别进行校正的多变量分析证实了这种关联，哮喘风险增加（比值比，3.06；95%置信区间，1.28 - 7.32；P值=0.012）。CCT CCC双倍型与哮喘相关（P值<0.0001；比值比，1.15；95%置信区间，1.07 - 1.23），特别是与过敏性哮喘相关（P值<0.0001）。CCT CCC双倍型是明确的。所有携带这种双倍型的个体都患有哮喘。
我们鉴定出一种可能与哮喘相关的PTGDR特异性启动子变异。这种双倍型是最近描述的两种转录效率最高的单倍型的组合。我们的体内研究结果将首次支持体外关于哮喘中PTGDR高转录效率单倍型的研究结果。
