The SERPINE2 gene is associated with chronic obstructive pulmonary disease in two large populations

Guohua Zhu, Liling Warren, Jennifer Aponte, Amund Gulsvik, Per Bakke, Wayne H. Anderson, David A. Lomas, Edwin K. Silverman, Sreekumar G. Pillai, Alvar Agusti, Peter M.A. Calverley, Claudio F. Donner, Robert D. Levy, Barry J. Make, Peter D. Paré, Stephen I. Rennard, Jørgen Vestbo, Emiel F.M. Wouters

Research output: Contribution to journalArticle

101 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number2
StatePublished - Jul 15 2007
Externally publishedYes


  • Chronic obstructive pulmonary disease
  • Genetic association, SERPINE2
  • Replication

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Zhu, G., Warren, L., Aponte, J., Gulsvik, A., Bakke, P., Anderson, W. H., Lomas, D. A., Silverman, E. K., Pillai, S. G., Agusti, A., Calverley, P. M. A., Donner, C. F., Levy, R. D., Make, B. J., Paré, P. D., Rennard, S. I., Vestbo, J., & Wouters, E. F. M. (2007). The SERPINE2 gene is associated with chronic obstructive pulmonary disease in two large populations. American Journal of Respiratory and Critical Care Medicine, 176(2), 167-173.