The role of WWOX polymorphisms on COPD susceptibility and pulmonary function traits in Chinese: a case-control study and family-based analysis.

Chenli Xie,Lisha Zhang,Di Wu,Xiaoliang Chen,Lei Yang,Jiansong Chen,Jiachun Lu,Fuman Qiu

doi:10.1038/srep21716

Abstract

Single nucleotide polymorphisms (SNPs) in the WW domain containing oxidoreductase (WWOX) gene were recently identified to be quantitative trait loci for lung function and thus likely to be susceptible biomarkers for COPD. However, the associations between WWOX SNPs and COPD risk are still unclear. Here, by conducting a two-center case-control study including 1511 COPD cases and 1677 controls and a family-based analysis comprising 95 nuclear pedigrees, we tested the associations between five SNPs that are rs10220974C >T, rs3764340C >G, rs12918952G >A, rs383362G >T, rs12828G >A of WWOX and COPD risk as well as the hereditary inclination of these loci among COPD families. We found that the SNP rs383362G >T was significantly associated with an increased risk of COPD in a T allele-number dependent-manner (OR = 1.30, 95%CI = 1.11 - 1.52). The T allele was more prone to over transmit to sick children and sibs than the G allele (Z = 2.900, P = 0.004). Moreover, the forced expiratory volume in one second/forced vital capacity (FEV1/FVC), FEV1/predicted-FEV1 and annual FEV1 also significantly decreased in the rs383362T carriers compared to the rs383362GG carriers. For other SNPs, no significant association was observed for COPD and pulmonary function. Taken together, our data demonstrated that the SNP rs383362G >T of WWOX plays a role in COPD inheritance.

Highlights

Chronic obstructive pulmonary disease (COPD) is one of the most strikingly increasing lung diseases characterized by incompletely reversible airflow obstruction
Two genome-wide association studies (GWASs) conducted in European reported that single nucleotide polymorphisms (SNPs), which are located in the WW domain containing oxidoreductase (WWOX) gene, were significantly associated with pulmonary function traits including the forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC15,16
In the current study, based on a two-stage case-control and a family-based study, we found that the T genotypes of WWOX SNP rs383362G > T were significantly associated with an increased risk of COPD and decreased pulmonary function traits in Chinese

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is one of the most strikingly increasing lung diseases characterized by incompletely reversible airflow obstruction. The pathogenesis of COPD is complex involving both environmental and genetic factors Environmental factors such as tobacco smoking and air pollution can cause a series of sophisticated biological reactions like oxidative stress to induce COPD development, while genetic variants can regulate the expression or function of such molecules participating in above reactions and determinate COPD susceptibility[3]. Due to different genetic background, different smokers show significantly different expression or function of these enzymes[10,11,12] In this condition, genetic variants located in these antioxidant enzymes might alter individuals’ susceptibility to develop COPD12–14. WWOX plays important roles in the regulation of a wide variety of cellular functions such as protein degradation, transcription and RNA splicing Stimulus such as tobacco smoking can directly trigger oxidative stress by virtue of decrease in WWOX expression[7]. These evidences suggest the WWOX gene to be a susceptible gene of COPD

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