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

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 SNIP analyses. Conclusions: These data provide further support for SERPINE2 as a COPD susceptibility gene.