Amerindian Ancestry Influences Genetic Susceptibility to Chronic Obstructive Pulmonary Disease

Roberto Díaz-Peña,Felix Boekstegers,Marc Miravitlles,Àlvar Agustí,Rafael S Silva,H Dean Hosgood,Sergio Jaime,Jordi Olloquequi,Justo Lorenzo Bermejo

doi:10.3390/jpm10030093

Abstract

The contribution of genetic ancestry on chronic obstructive pulmonary disease (COPD) predisposition remains unclear. To explore this relationship, we analyzed the associations between 754,159 single nucleotide polymorphisms (SNPs) and risk of COPD (n = 214 cases, 193 healthy controls) in Talca, Chile, considering the genetic ancestry and established risk factors. The proportion of Mapuche ancestry (PMA) was based on a panel of 45 Mapuche reference individuals. Five PRDM15 SNPs and two PPP1R12B SNPs were associate with COPD risk (p = 0.05 to 5 × 10−4) in those individuals with lower PMA. Based on linkage disequilibrium and sliding window analyses, an adjacent PRDM15 SNPs were associated with COPD risk in the lower PMA group (p = 10−3 to 3.77 × 10−8). Our study is the first to report an association between PPP1R12B and COPD risk, as well as effect modification between ethnicity and PRDM15 SNPs in determining COPD risk. Our results are biologically plausible given that PPP1R12B and PRDM15 are involved in immune dysfunction and autoimmunity, providing mechanistic evidence for COPD pathogenesis and highlighting the importance to conduct more genome wide association studies (GWAS) in admixed populations with Amerindian descent.

Highlights

Chronic obstructive pulmonary disease (COPD) is a common disorder characterized by a persistent and progressive airflow limitation that is associated with an enhanced chronic inflammatory response in the airways and lungs to noxious particles or gases, those attributed to cigarette and biomass smoke [1,2]
The present study is the first to report the contribution of established risk factors, genetic ancestry, and single nucleotide polymorphisms (SNPs) associated to COPD risk in a Latin American population, characterized by a large admixture of Amerindian ancestry
The higher exposure to biomass smoke could explain the fact that female COPD participants showed a decreased DLCO than men

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a common disorder characterized by a persistent and progressive airflow limitation that is associated with an enhanced chronic inflammatory response in the airways and lungs to noxious particles or gases, those attributed to cigarette and biomass smoke [1,2]. According to the World Health Organization, approximately 3 million people in the world die as a consequence of COPD every year, and the disease burden is increasing in Latin America [4]. Latin American countries experience a COPD prevalence of 13.4%, with in-hospital mortality rate ranging from 6.7% to 29.5% [5]. The prevalence of COPD increases steeply with age, with the highest prevalence among those people over 60 years [6]. Considering the high rates of tobacco use and biomass burning in several Latin American countries [7,8], COPD may become an even greater health problem in Latin America than previously hypothesized. In Chile, for example, respiratory diseases are the third most common cause of death, with COPD accounting for 22% of the deaths and being the second cause of decease [9]

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Conclusion