Participation of HHIP Gene Variants in COPD Susceptibility, Lung Function, and Serum and Sputum Protein Levels in Women Exposed to Biomass-Burning Smoke.

Alejandro Ortega-Martínez,Espiridión Ramos-Martínez,Ramcés Falfán-Valencia,Edgar Abarca-Rojano,María Elena Ramírez-Díaz,Filiberto Cruz-Vicente,María De Lourdes Martínez-Gómez,Alejandra Ramírez-Venegas,Gloria Pérez-Rubio

doi:10.3390/diagnostics10100734

Abstract

Background: A variety of organic materials (biomass) are burned for cooking and heating purposes in poorly ventilated houses; smoke from biomass combustion is considered an environmental risk factor for chronic obstructive pulmonary disease COPD. In this study, we attempted to determine the participation of single-nucleotide variants in the HHIP (hedgehog-interacting protein) gene in lung function, HHIP serum levels, and HHIP sputum supernatant levels in Mexican women with and without COPD who were exposed to biomass-burning smoke. Methods: In a case-control study (COPD-BS, n = 186, BBES, n = 557) in Mexican women, three SNPs (rs13147758, rs1828591, and rs13118928) in the HHIP gene were analyzed by qPCR; serum and supernatant sputum protein levels were determined through ELISA. Results: The rs13118928 GG genotype is associated with decreased risk (p = 0.021, OR = 0.51, CI95% = 0.27–0.97) and the recessive genetic model (p = 0.0023); the rs1828591-rs13118928 GG haplotype is also associated with decreased risk (p = 0.04, OR = 0.65, CI95% 0.43–0.98). By the dominant model (rs13118928), the subjects with one or two copies of the minor allele (G) exhibited higher protein levels. Additionally, two correlations with the AG genotype were identified: BBES with FEV1 (p = 0.03, r2 = 0.53) and COPD-BS with FEV1/FVC (p = 0.012, r2 = 0.54). Conclusions: Single-nucleotide variants in the HHIP gene are associated with decreased COPD risk, higher HHIP serum levels, and better lung function in Mexican women exposed to biomass burning.

Highlights

Chronic obstructive pulmonary disease (COPD) is a common and tractable pathology characterized by persistent respiratory symptoms and limited airflow; these symptoms are commonly caused by significant exposure to noxious particles or gases [1]
COPD is classified as a multifactorial disease, which means that in addition to the environmental factors strongly associated with the physiopathology of the disease, genetic factors, mostly single nucleotide polymorphisms (SNPs), have been determined to contribute to the susceptibility and clinical variables of COPD [6]
We attempted to determine the participation of single-nucleotide variants in the HHIP gene in lung function, HHIP serum levels, and HHIP sputum supernatant levels in Mexican women with and without COPD who were exposed to biomass-burning smoke

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a common and tractable pathology characterized by persistent respiratory symptoms and limited airflow; these symptoms are commonly caused by significant exposure to noxious particles or gases [1]. In 2009, through genome-wide association studies (GWAS), several SNPs in the HHIP (hedgehog-interacting protein) gene were identified [7]; in this initial study, the results did not reach strict levels of significance. A variety of organic materials (biomass) are burned for cooking and heating purposes in poorly ventilated houses; smoke from biomass combustion is considered an environmental risk factor for chronic obstructive pulmonary disease COPD. We attempted to determine the participation of single-nucleotide variants in the HHIP (hedgehog-interacting protein) gene in lung function, HHIP serum levels, and HHIP sputum supernatant levels in Mexican women with and without COPD who were exposed to biomass-burning smoke. Conclusions: Single-nucleotide variants in the HHIP gene are associated with decreased COPD risk, higher HHIP serum levels, and better lung function in Mexican women exposed to biomass burning

Methods

Results

Conclusion