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Meta-analyses on Suspected Chronic Obstructive Pulmonary Disease Genes

A Summary of 20 Years' Research

¹ Department of Genetics, ² Department of Pulmonology, and ³ Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Correspondence and requests for reprints should be addressed to Prof. H. M. Boezen, Ph.D., Unit Chronic Airway Diseases (Head), Dept. of Epidemiology E3.29, University Medical Center Groningen, Groningen P.O. Box 30.001 9700 RB Groningen, The Netherlands. E-mail: h.m.boezen{at}epi.umcg.nl

Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disorder with high mortality worldwide. Studies on the role of candidate genes and their polymorphisms in COPD development have so far produced ambiguous results.

Objectives: The aim of this study was to reveal the role of COPD candidate genes using data collected in previous research.

Methods: We performed meta-analyses on 20 polymorphisms in 12 genes, after searching the PubMed and Embase databases for publications on COPD. These genes involve three main pathways associated with COPD development: the inflammatory, protease–antiprotease balance, and antioxidant pathways.

Measurements and Main Results: We obtained significant results for three TGFB1 polymorphisms, although these were based only on a few studies. The IL1RN VNTR polymorphism increases the risk for COPD (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.09–2.65), whereas the TNFA –308 G/A polymorphism does so only in Asian populations (OR, 2.01; 95% CI, 1.21–3.31). The GSTP1 I105V polymorphism was protective for COPD in Asian populations only (OR, 0.69; 95% CI, 0.56–0.85).

Conclusions: These results demonstrate the importance of ethnicity in identifying specific COPD genes.

Key Words: chronic obstructive pulmonary disease • genes • polymorphism • single nucleotide polymorphisms • meta-analysis • ethnicity

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject For many years only one chronic obstructive pulmonary disease gene was known. Searching for additional genes was based on candidate gene studies, which often were impossible to replicate. What This Study Adds to the Field The choice of populations for a meta-analysis study or replication can strongly affect results for COPD candidate genes, as at least some of the associations have opposite directions.

 

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