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ADRB2(肾上腺素能受体β2)基因多态性对南印度支气管哮喘患者哮喘发生及雾化沙丁胺醇反应的影响。

Effect of ADRB2 (adrenergic receptor β2) gene polymorphisms on the occurrence of asthma and on the response to nebulized salbutamol in South Indian patients with bronchial asthma.

作者信息

Shah Neel Jayesh, Vinod Kumar Saka, Gurusamy Umamaheswaran, Annan Sudarsan Arun Kumar, Shewade Deepak Gopal

机构信息

a Department of Pharmacology and.

出版信息

J Asthma. 2015 Oct;52(8):755-62. doi: 10.3109/02770903.2015.1012589. Epub 2015 May 19.

Abstract

INTRODUCTION

Genetic mutations in the β2 receptor could alter its functioning and the response to β2 agonists. The study was done to find out the effect of two commonly occurring polymorphisms-Arg16Gly and Gln27Glu, on cause of asthma and on response to nebulized salbutamol in South Indian subjects of asthma.

METHODS

After baseline measurements of Forced Expiratory Volume in 1st second (FEV1), Forced Vital Capacity (FVC) and Peak Expiratory Flow Rate (PEFR), five mg of nebulized salbutamol was administered and spirometry was repeated. The increase in these parameters was calculated and patients were included for genotyping if the percentage increase in FEV1 was ≥12%. The frequencies of these polymorphisms in patients were compared with those of healthy volunteers.

RESULTS

112 patients and 127 healthy volunteers were genotyped. The frequencies of the polymorphisms were found to be similar to previously published Dravidian population frequencies. The frequencies of genotypes in asthmatics were similar to healthy volunteers. The increase in FEV1, FVC and PEFR was similar across various genotypes and haplotypes in both the polymorphisms. The GG-CG haplotype was associated with 3.1 times increased occurrence of asthma (p value = 0.02). The G allele of the Arg16Gly polymorphism was associated with lower baseline FEV1, FVC and PEFR values, but these were not statistically significant.

CONCLUSION

The Arg16Gly and Gln27Glu polymorphisms do not determine the occurrence of asthma individually, but the GG-CG haplotype is associated with an increased risk of asthma. There is no effect of the genotypes on the response to nebulized salbutamol.

摘要

引言

β2受体中的基因突变可能会改变其功能以及对β2激动剂的反应。本研究旨在探究两种常见的多态性——精氨酸16位点甘氨酸突变(Arg16Gly)和谷氨酰胺27位点谷氨酸突变(Gln27Glu),对南印度哮喘患者哮喘病因及雾化吸入沙丁胺醇反应的影响。

方法

在测量第一秒用力呼气容积(FEV1)、用力肺活量(FVC)和呼气峰值流速(PEFR)的基线值后,给予5毫克雾化沙丁胺醇,然后重复进行肺功能测定。计算这些参数的增加值,如果FEV1的增加值百分比≥12%,则将患者纳入基因分型。将患者中这些多态性的频率与健康志愿者的频率进行比较。

结果

对112例患者和127名健康志愿者进行了基因分型。发现这些多态性的频率与先前公布的达罗毗荼人群频率相似。哮喘患者的基因型频率与健康志愿者相似。在这两种多态性中,不同基因型和单倍型的FEV1、FVC和PEFR的增加值相似。GG - CG单倍型与哮喘发生率增加3.1倍相关(p值 = 0.02)。Arg16Gly多态性的G等位基因与较低的FEV1、FVC和PEFR基线值相关,但差异无统计学意义。

结论

Arg16Gly和Gln27Glu多态性单独并不决定哮喘的发生,但GG - CG单倍型与哮喘风险增加相关。基因型对雾化吸入沙丁胺醇的反应没有影响。

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