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前列腺素E2受体EP3亚型基因(Ptger3)的遗传变异与韩国人群哮喘之间的关联。

Association between genetic variations in prostaglandin E2 receptor subtype EP3 gene (Ptger3) and asthma in the Korean population.

作者信息

Park H-W, Shin E-S, Lee J-E, Kim S-H, Kim S-S, Chang Y-S, Kim Y-K, Min K-U, Kim Y-Y, Cho S-H

机构信息

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Clin Exp Allergy. 2007 Nov;37(11):1609-15. doi: 10.1111/j.1365-2222.2007.02820.x. Epub 2007 Sep 17.

Abstract

BACKGROUND

Recent investigations suggest that prostaglandin E2 (PGE2) is important in the pathogenesis of not only aspirin-intolerant asthma but also asthma unrelated to aspirin intolerance.

OBJECTIVES

This study was conducted to evaluate the effects of variations in the gene coding PGE2 receptor subtype EP1-4 (Ptger1-4) on the risk of asthma in the Korean population.

METHODS

Nineteen single nucleotide polymorphisms (SNPs) were selected after re-sequencing Ptger1-4 and were genotyped in 480 asthmatics and 140 healthy controls, who were randomly recruited.

RESULTS

By logistic regression analyses controlling for age and sex, 1388T>C in Ptger3 was found to be significantly associated with asthma [P=0.002, odds ratio (95% confidence interval)=0.63 (0.46-0.85) in the allele model], and this remained significant after applying the Bonferroni correction. In terms of haplotype, the frequency of the C-C-A-A haplotype in Ptger3 was significantly lower in asthmatics than in healthy controls (P=0.004). Moreover, the prevalence of this haplotype was significantly lower in moderate-to-severe asthmatics than in mild asthmatics (P=0.045; mild vs. moderate and P=0.034; mild vs. severe). However, no association was found between any genetic variation in Ptger1, Ptger2, or Ptger4 and asthma.

CONCLUSION

The present study demonstrated that genetic variations in Ptger3 are significantly associated with the risk and severity of asthma in the Korean population.

摘要

背景

最近的研究表明,前列腺素E2(PGE2)不仅在阿司匹林不耐受性哮喘的发病机制中起重要作用,而且在与阿司匹林不耐受无关的哮喘中也起重要作用。

目的

本研究旨在评估编码PGE2受体亚型EP1 - 4(Ptger1 - 4)的基因变异对韩国人群哮喘风险的影响。

方法

在对Ptger1 - 4进行重测序后选择了19个单核苷酸多态性(SNP),并在随机招募的480名哮喘患者和140名健康对照中进行基因分型。

结果

通过对年龄和性别进行校正的逻辑回归分析,发现Ptger3中的1388T>C与哮喘显著相关[在等位基因模型中,P = 0.002,优势比(95%置信区间)= 0.63(0.46 - 0.85)],在应用Bonferroni校正后该结果仍然显著。就单倍型而言,Ptger3中C - C - A - A单倍型的频率在哮喘患者中显著低于健康对照(P = 0.004)。此外,该单倍型在中重度哮喘患者中的患病率显著低于轻度哮喘患者(轻度与中度相比,P = 0.045;轻度与重度相比,P = 0.034)。然而,未发现Ptger1、Ptger2或Ptger4中的任何基因变异与哮喘之间存在关联。

结论

本研究表明,Ptger3中的基因变异与韩国人群哮喘的风险和严重程度显著相关。

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