<p>Evaluation Of <em>HHIP</em> Polymorphisms And Their Relationship With Chronic Obstructive Pulmonary Disease Phenotypes</p>

Abstract

PurposeWe 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 methodsA 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.ResultsAn 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.ConclusionThe presence of the A allele in the rs13118928 polymorphism of the HHIP gene may be related to the emphysema-hyperinflation phenotype.

Sonic hedgehog signalling as a potential endobronchial biomarker in COPD

“…Gli2 may be found in basal AEC nuclei, but can also be observed subciliary in ciliated cells, suggesting the presence of autocrine and paracrine signalling in the epithelium. We then focused on Hhip, another Shh receptor acting as an inhibitor of HH signalling, which is particularly interesting, as genetic alteration of Hhip was associated with COPD and emphysema in genome-wide associated studies and murine models [4,5,[31][32][33][34][35]. We detected Hhip in differentiated cells, but the absence of differential Hhip localization between non-COPD and COPD samples suggested that genetic alterations of Hhip may impact protein function rather than protein expression.…”

The SNP rs13118928, rs1828591 and rs10519717 in the HHIP Gene are not Associated on COPD Susceptibility in Male Javanese Smokers

“…Mice with haploinsufficiency (HHIP +/-) are more susceptible to developing severe emphysema due to exposure to cigarette smoke than wild type mice (HHIP +/-) (5) . In this study, it was found that the presence of polymorphisms in the HHIP gene at positions rs13118928, rs1828591 and rs10519717 did not make Javanese smokers susceptible to COPD (16) . (8,9,17) and in Mongolians (10) .…”

The SNP rs13147758 in the HHIP Gene Is Associated With COPD Susceptibility, Serum, and Sputum Protein Levels in Smokers

“…For rs1828591, one of the most highly associated polymorphisms in other populations (Lamontagne et al, 2013;Kerkhof et al, 2014;Bártholo et al, 2019), the case-control analysis showed that AA COPD patients have higher protein levels than control subjects. Serum protein levels analyzed in the dominant model confirmed an association with the AA genotype in the COPD-TS group (AA vs. AG + GG).…”