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Published ahead of print on April 19, 2007, doi:10.1164/rccm.200611-1723OC
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American Journal of Respiratory and Critical Care Medicine Vol 176. pp. 167-173, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200611-1723OC

Original Article

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

Guohua Zhu1, Liling Warren1, Jennifer Aponte1, Amund Gulsvik2, Per Bakke2, The International COPD Genetics Network (ICGN) Investigators*, Wayne H. Anderson1, David A. Lomas3, Edwin K. Silverman4 and Sreekumar G. Pillai1

1 GlaxoSmithKline, Research Triangle Park, North Carolina; 2 University of Bergen, Bergen, Norway; 3 Cambridge Institute for Medical Research, Cambridge, United Kingdom; and 4 Brigham and Women's Hospital, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Sreekumar G. Pillai, Ph.D., GlaxoSmithKline R&D, 5 Moore Drive, Research Triangle Park, NC 27709. 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 the chromosome 2q region SERPINE2 (Serpin peptidase inhibitor, clade E [nexin, plasminogen activator inhibitor type 1], member 2), was previously evaluated as a susceptibility gene for COPD 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 1,910 individuals and an independent case-control population that included 973 COPD cases and 956 control subjects. The family data were analyzed using family-based association tests. The case-control data were analyzed using logistic regression and linear models.

Measurements and 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: chronic obstructive pulmonary disease • genetic association, SERPINE2 • replication


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
A positional candidate gene from the chromosome 2q region SERPINE2 (Serpin peptidase inhibitor, clade E [nexin, plasminogen activator inhibitor type 1], member 2), was previously evaluated as a susceptibility gene for COPD in two association studies, but the results were contradictory.

What This Study Adds to the Field
SERPINE2 demonstrates significant positive association with COPD phenotypes.

 



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