Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma

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Abstract

Background

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.

Methods

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.

Results

−197T>C polymorphism was significantly associated with asthma [Fisher's P-value = 0.007, Monte Carlo P-value (104 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.

Conclusion

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.

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