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 Israel Rennard, Jørgen Vestbo, Emiel F.M. Wouters

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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
Volume176
Issue number2
DOIs
StatePublished - Jul 15 2007

Fingerprint

Chronic Obstructive Pulmonary Disease
Population
Genes
Single Nucleotide Polymorphism
Phenotype
Serpin E2
Chromosomes
Logistic Models
Plasminogen Activator Inhibitor 1
Disease Susceptibility
Pedigree
Haplotypes
Case-Control Studies
Linear Models

Keywords

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

ASJC Scopus subject areas

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

Cite this

The SERPINE2 gene is associated with chronic obstructive pulmonary disease in two large populations. / Zhu, Guohua; Warren, Liling; Aponte, Jennifer; Gulsvik, Amund; Bakke, Per; Anderson, Wayne H.; Lomas, David A.; Silverman, Edwin K.; Pillai, Sreekumar G.; Agusti, Alvar; Calverley, Peter M.A.; Donner, Claudio F.; Levy, Robert D.; Make, Barry J.; Paré, Peter D.; Rennard, Stephen Israel; Vestbo, Jørgen; Wouters, Emiel F.M.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 176, No. 2, 15.07.2007, p. 167-173.

Research output: Contribution to journalArticle

Zhu, G, Warren, L, Aponte, J, Gulsvik, A, Bakke, P, Anderson, WH, Lomas, DA, Silverman, EK, Pillai, SG, Agusti, A, Calverley, PMA, Donner, CF, Levy, RD, Make, BJ, Paré, PD, Rennard, SI, Vestbo, J & Wouters, EFM 2007, 'The SERPINE2 gene is associated with chronic obstructive pulmonary disease in two large populations', American Journal of Respiratory and Critical Care Medicine, vol. 176, no. 2, pp. 167-173. https://doi.org/10.1164/rccm.200611-1723OC
Zhu, Guohua ; Warren, Liling ; Aponte, Jennifer ; Gulsvik, Amund ; Bakke, Per ; Anderson, Wayne H. ; Lomas, David A. ; Silverman, Edwin K. ; Pillai, Sreekumar G. ; Agusti, Alvar ; Calverley, Peter M.A. ; Donner, Claudio F. ; Levy, Robert D. ; Make, Barry J. ; Paré, Peter D. ; Rennard, Stephen Israel ; Vestbo, Jørgen ; Wouters, Emiel F.M. / The SERPINE2 gene is associated with chronic obstructive pulmonary disease in two large populations. In: American Journal of Respiratory and Critical Care Medicine. 2007 ; Vol. 176, No. 2. pp. 167-173.
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abstract = "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.",
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AU - Warren, Liling

AU - Aponte, Jennifer

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AU - Bakke, Per

AU - Anderson, Wayne H.

AU - Lomas, David A.

AU - Silverman, Edwin K.

AU - Pillai, Sreekumar G.

AU - Agusti, Alvar

AU - Calverley, Peter M.A.

AU - Donner, Claudio F.

AU - Levy, Robert D.

AU - Make, Barry J.

AU - Paré, Peter D.

AU - Rennard, Stephen Israel

AU - Vestbo, Jørgen

AU - Wouters, Emiel F.M.

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N2 - 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.

AB - 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.

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