Association of SERPINE2 With Asthma

Abstract

A sthma and COPD are complex human airway diseases that are infl uenced by various genetic and environmental susceptibility factors. In 1961, Orie and colleagues 1 proposed that these diseases were different expressions of one basic pulmonary disease whose expression in individuals was shaped differently depending on a combination of endogenous (ie, host) and exogenous (ie, environmental) factors. This view, which became known as the "Dutch hypothesis," suggests that overlapping clinical features of asthma and COPD are partly based on an allergic diathesis and airways hyperresponsiveness (AHR). 2 Although there is some opposition to the original Dutch hypothesis, little doubt exists that common mechanisms underlie asthma and COPD. 3 Identifying genetic variants that infl uence some of these common mechanisms would provide important insights into both diseases.Genetic linkage studies of COPD, 4 asthma, 5,6 and general population lung function 7 have demonstrated linkage peaks on chromosome 2q, suggesting that in this region are good Dutch hypothesis candidate genes. This is further supported by linkage results observed on chromosome 2q for asthma and COPD being strongest for the FEV 1 /FVC phenotype. A promising Background: The "Dutch hypothesis" suggests that asthma and COPD have common genetic determinants. The serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 ( SERPINE2 ) gene previously has been associated with COPD. We sought to determine whether SERPINE2 is associated with asthma and asthma-related phenotypes. Methods: We measured the association of 39 SERPINE2 single-nucleotide polymorphisms (SNPs) with asthma-related phenotypes in 655 parent-child trios from the Childhood Asthma Management Program (CAMP), and we measured the association of 19 SERPINE2 SNPs with asthma in a case-control design of 359 CAMP probands and 846 population control subjects. We attempted to replicate primary asthma-related phenotype fi ndings in one independent population and primary asthma affection status fi ndings in two independent populations. We compared association results with CAMP proband expression quantitative trait loci.

Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes

“…39 Furthermore, some of the genes we have studied are associated not only with COPD but also with asthma. [40][41][42] We cannot fully exclude that observed associations with lung function in our birth cohort might be ascribed to asthma. However, this is unlikely because none of the SNPs were associated with doctor-diagnosed asthma at age 8 years (data not shown).…”

Increased expression of protease nexin-1 in fibroblasts during idiopathic pulmonary fibrosis regulates thrombin activity and fibronectin expression

“…10,35 Some PN-1 variants have been associated with lung function among patients with COPD and asthma. 36 We thus propose that PN-1 is a new important player in pulmonary fibrosis and hypothesize that the biological activity of PN-1 could be of importance in the progression of the pathology. Such a role could be deleterious, regarding the impact of PN-1 on the induction of ECM proteins such as fibronectin or, in contrast, beneficial in view of the impact of PN-1 on thrombin activity.…”

Association of Forced Vital Capacity with the Developmental Gene NCOR2

“…SERPINE2 is a member of a gene family encoding serpins, highly conserved proteins that help maintain tissue integrity by controlling the activity of proteases in diverse biological processes, in particular by inhibiting serine proteases such as trypsin. SERPINE2 has a known link to airway obstruction, with strong evidence of association with COPD[ 34 ] and some evidence of association with childhood asthma[ 35 ]. Our findings support an association with a marker of lung restriction too, FVC, in both adults and children, in line with previous findings of an association with FVC in children that could not be replicated[ 36 ].…”