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

Alejandro Ortega-Martínez,Karol J Nava-Quiroz,Rafael De Jesus Hernández-Zenteno,Gloria Pérez-Rubio,Alejandra Ramírez-Venegas,Edgar Abarca-Rojano,Andrea Hernández-Pérez,Sebastián Rodríguez-Llamazares,Ramcés Falfán-Valencia,Leonor García-Gómez,Enrique Ambrocio-Ortiz

doi:10.3389/fgene.2020.00882

Abstract

BackgroundGenetic association studies have identified single nucleotide polymorphisms (SNPs) related to chronic obstructive pulmonary disease (COPD) susceptibility. The aim of this study was to identify HHIP genetic variants associated with COPD, pulmonary function, and serum and sputum HHIP protein levels in Mexican mestizo smokers.Materials and MethodsAssociation analysis was performed by carrying out a case–control study in Mexican mestizo smokers comprised of two groups: tobacco-smoking subjects with COPD (COPD-TS, n = 222) and smokers without COPD (SWOC, n = 333). We evaluated three SNPs (rs13147758, rs1828591, and rs13118928) in the HHIP gene. Allele discrimination was accomplished by qPCR using TaqMan probes, and determination of protein levels in the serum and sputum supernatants (SS) was performed using ELISA.ResultsStatistically significant differences were observed in the rs13147758 GG genotype (adjusted p = 0.014, OR = 1.95) and the rs13147758-rs1828591 GA haplotype (p = 6.6E-06, OR = 2.65) in the case–control comparison. HHIP protein levels were elevated in SS samples from the COPD-TS group compared to those from the SWOC group (p = 0.03). Based on genotype analysis, HHIP protein levels were lower in the serum samples of rs13147758 GG genotype carriers in the COPD-TS group than in the serum samples of rs13147758 GG genotype carriers from the SWOC group (p < 0.05), but there were no differences in the sputum samples.ConclusionThe rs13147758 GG genotype and the rs13147758-rs1828591 GA haplotype are associated with susceptibility to COPD. Furthermore, an association in protein levels was observed between the HHIP rs13147758 genotype and COPD in Mexican mestizo smokers.

Highlights

Tobacco smoking (TS) is considered the leading risk factor for the development of chronic obstructive pulmonary disease (COPD), as approximately 50% of COPD cases worldwide are related to TS (Lamprecht et al, 2011; Bajpai et al, 2019)
For smoking onset, smokers with COPD started smoking at an earlier age than smokers without the disease, the difference was not statistically significant (p = 0.208)
Of the three evaluated polymorphisms in Mexican mestizo smokers, rs13147758 was associated with susceptibility to COPD and reduced lung function values among smokers

Summary

Introduction

Tobacco smoking (TS) is considered the leading risk factor for the development of chronic obstructive pulmonary disease (COPD), as approximately 50% of COPD cases worldwide are related to TS (Lamprecht et al, 2011; Bajpai et al, 2019). Only 15–20% of smokers develop the disease, and previous studies suggest that genetic variants contribute to COPD susceptibility (Nakamura, 2011). Through genome-wide association studies (GWAS), it is possible to examine millions of genetic variants, mostly single nucleotide polymorphisms (SNPs), and to identify different genomic regions related to pulmonary function traits, emphysema, and several phenotypes of COPD (Hobbs and Hersh, 2014). We aimed to identify possible associations between three SNPs (rs13147758, rs13118928, and rs1828591) in the HHIP gene and COPD susceptibility, pulmonary function traits, and HHIP protein levels in the serum and sputum in Mexican mestizo smokers. The aim of this study was to identify HHIP genetic variants associated with COPD, pulmonary function, and serum and sputum HHIP protein levels in Mexican mestizo smokers

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