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

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

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00882

DOI=10.3389/fgene.2020.00882

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>Genetic association studies have identified single nucleotide polymorphisms (SNPs) related to chronic obstructive pulmonary disease (COPD) susceptibility. The aim of this study was to identify <italic>HHIP</italic> genetic variants associated with COPD, pulmonary function, and serum and sputum HHIP protein levels in Mexican mestizo smokers.</p></sec><sec><title>Materials and Methods</title><p>Association 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, <italic>n</italic> = 222) and smokers without COPD (SWOC, <italic>n</italic> = 333). We evaluated three SNPs (rs13147758, rs1828591, and rs13118928) in the <italic>HHIP</italic> 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.</p></sec><sec><title>Results</title><p>Statistically significant differences were observed in the rs13147758 GG genotype (adjusted <italic>p</italic> = 0.014, OR = 1.95) and the rs13147758-rs1828591 GA haplotype (<italic>p</italic> = 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 (<italic>p</italic> = 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 (<italic>p</italic> &lt; 0.05), but there were no differences in the sputum samples.</p></sec><sec><title>Conclusion</title><p>The 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 <italic>HHIP</italic> rs13147758 genotype and COPD in Mexican mestizo smokers.</p></sec>