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<or=p<or=0.042). Five of these SNPs demonstrated replicated associations in the case-control analysis (0.021<or=p<or=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.
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<or=p<or=0.042). Five of these SNPs demonstrated replicated associations in the case-control analysis (0.021<or=p<or=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.
Authors: Emily S Wan; Michael H Cho; Nadia Boutaoui; Barbara J Klanderman; Jody S Sylvia; John P Ziniti; Sungho Won; Christoph Lange; Sreekumar G Pillai; Wayne H Anderson; Xiangyang Kong; David A Lomas; Per S Bakke; Amund Gulsvik; Elizabeth A Regan; James R Murphy; Barry J Make; James D Crapo; Emiel F Wouters; Bartolome R Celli; Edwin K Silverman; Dawn L DeMeo Journal: Am J Respir Cell Mol Biol Date: 2010-10-29 Impact factor: 6.914
Authors: Peter J Castaldi; Michael H Cho; Augusto A Litonjua; Per Bakke; Amund Gulsvik; David A Lomas; Wayne Anderson; Terri H Beaty; John E Hokanson; James D Crapo; Nan Laird; Edwin K Silverman Journal: Am J Respir Cell Mol Biol Date: 2011-06-09 Impact factor: 6.914
Authors: Michael H Cho; George R Washko; Thomas J Hoffmann; Gerard J Criner; Eric A Hoffman; Fernando J Martinez; Nan Laird; John J Reilly; Edwin K Silverman Journal: Respir Res Date: 2010-03-16
Authors: Ceri E Stewart; Ian P Hall; Stuart G Parker; Miriam F Moffat; Andrew J Wardlaw; Martin J Connolly; Charlotte Ruse; Ian Sayers Journal: BMC Med Genet Date: 2009-10-31 Impact factor: 2.103