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Published ahead of print on April 19, 2007, doi:10.1164/rccm.200611-1723OC

Am. J. Respir. Crit. Care Med., Volume 176, Number 2, July 2007, 167-173

A more recent version of this article appeared on July 15, 2007
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Submitted on November 28, 2006
Accepted on April 19, 2007

The SERPINE2 Gene is Associated with Chronic Obstructive Pulmonary Disease in Two Large Populations

Guohua Zhu1, Liling Warren1, Jennifer Aponte1, Amund Gulsvik2, Per Bakke2, ICGN Investigators, Wayne H Anderson1, David A Lomas3, Edwin K Silverman4, and Sreekumar G Pillai1*

1 Glaxo SmithKline, Research Triangle Park, NC, USA, 2 University of Bergen, Bergen, Norway, 3 Cambridge Institue for Medical Research, Cambridge, United Kingdom, 4 Brigham and Women's Hospital, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: sreekumar.g.pillai{at}gsk.com.

Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by multiple genes and environmental factors. A region on chromosome 2q has been shown to be linked to COPD. A positional candidate gene from this region, SERPINE2, was previously evaluated as a susceptibility gene in two association studies, but the results were contradictory. Objectives: To identify the relationship between SERPINE2 polymorphisms and COPD-related phenotypes using family-based and case-control association studies. Methods: In the present study, we genotyped 25 single nucleotide polymorphisms (SNPs) from SERPINE2 and analyzed qualitative and quantitative COPD phenotypes in 635 pedigrees with 1910 individuals and an independent case-control population which included 973 COPD cases and 956 controls. The family data were analyzed using family-based association tests. The case-control data were analyzed using logistic regression and linear models. Main Results: Six SNPs demonstrated significant associations with COPD phenotypes in the family-based association analysis (0.0016≤P≤0.042). Five of these SNPs demonstrated replicated associations in the case-control analysis (0.021≤P≤0.031). In addition, the results of haplotype analyses supported the results from single SNP analyses. Conclusions: These data provide further support for SERPINE2 as a COPD susceptibility gene.
Key words: COPD, genetic association, SERPINE2, replication




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