Evaluation Of HHIP Polymorphisms And Their Relationship With Chronic Obstructive Pulmonary Disease Phenotypes
Evaluation Of HHIP Polymorphisms And Their Relationship With Chronic Obstructive Pulmonary Disease Phenotypes
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DOI：
10.2147/copd.s213519
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发表时间：
2019-01-01
影响因子：
2.8
通讯作者：
Da Costa, Claudia Henrique
中科院分区：
文献类型：
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作者：
Bartholo, Thiago Prudente;Porto, Luis Cristovio;Da Costa, Claudia Henrique
目的：我们旨在将刺猬相互作用蛋白（hip）基因的三种多态性与慢性阻塞性肺疾病的三种主要表型（频繁加重症（FE）、哮喘/COPD重叠症（ACO）和肺气肿伴恶性膨胀）联系起来。患者和方法：2015年2月至2018年7月，在巴西里约热内卢州立大学肺内科进行了一项横断面研究。根据慢性阻塞性肺疾病全球倡议（GOLD）的标准，共有81名诊断为COPD的患者入组。受试者根据其表型分为三组（FE， ACO和肺气肿-恶性膨胀）。研究人员分析了常被报道为参与COPD发病机制的hip基因的三个多态性：rs1828591、rs13118928和rs6537296。进行实时PCR - TAQMAN SNP基因分型试验。统计分析采用SPSS程序进行，采用多变量分析，置信区间为95%。结果：COPD合并肺气肿-恶性膨胀表型组的rs13118928 HHIP基因多态性A等位基因频率高于FE表型组（p=0.019）和ACO组（p=0.04）。然而，具有肺气肿-恶性膨胀表型的受试者更常出现A等位基因（p=0.04）。基因型分析证实了肺气肿-恶性膨胀和ACO表型之间的差异，肺气肿-恶性膨胀组AA基因型的患病率更高（p=0.04）。ACO和FE表型的受试者在这些多态性上没有差异。rs1828591多态性（p= 0.552）和rs6537296多态性（p=0.296）在三种表型中无显著差异。结论：hip基因rs13118928多态性中A等位基因的存在可能与肺气肿-恶性膨胀表型有关。
Purpose: We aimed to correlate three polymorphisms of the Hedgehog Interacting Protein (HHIP) gene with the three main phenotypes of the chronic obstructive pulmonary disease (frequent exacerbator (FE), asthma/COPD overlap (ACO), and emphysema with hyperinflation).Patients and methods: A cross-sectional study was carried out in the Department of Pulmonology at the Rio de Janeiro State University from February 2015 to July 2018. A total of 81 patients diagnosed with COPD according to the criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) were enrolled. The subjects were divided into three distinct groups according to their phenotypes (FE, ACO and emphysema-hyperinflation). Three polymorphisms of the HHIP gene that are often reported as allegedly involved in the pathogenesis of COPD were analysed: rs1828591, rs13118928, and rs6537296. Real-time PCR - TAQMAN SNP Genotyping Assay was performed. The statistical analysis was carried out with the SPSS program with a multivariate analysis with a 95% confidence interval.Results: An increase in the frequency of the A allele of the rs13118928 HHIP gene polymorphism was observed in the group of subjects with COPD and emphysema-hyperinflation phenotype when compared with those in the FE phenotype (p=0.019) and subjects with ACO (p=0.04). However, the subjects with emphysema-hyperinflation phenotype presented more often the A allele (p=0.04). The genotypic analysis confirmed the difference between the emphysema-hyperinflation and ACO phenotypes, with a higher prevalence of the AA genotype in the emphysema-hyperinflation group (p=0.04). The ACO and FE phenotype subjects showed no difference in these polymorphisms. No difference was found in the frequency of the polymorphisms rs1828591 (p= 0.552) and rs6537296 (p=0.296) in the three phenotypes evaluated.Conclusion: The presence of the A allele in the rs13118928 polymorphism of the HHIP gene may be related to the emphysema-hyperinflation phenotype.