A Role for Wnt Signaling Genes in the Pathogenesis of Impaired Lung Function in Asthma

• DOI: 10.1164/rccm.200907-1009oc
• Publication Date: 2009-11-20T03:34:44Z
• Authors: Sunita Sharma; Kelan Tantisira; Vincent Carey; Amy J. Murphy; Jessica Lasky-Su; Juan C. Celedón; Ross Lazarus; Barbara Klanderman; Angela Rogers; Manuel Soto-Quirós; Lydiana Avila; Thomas Mariani; Roger Gaedigk; Stephen Leeder; John Torday; David Warburton; Benjamin Raby; Scott T. Weiss
• Keywords: Candidate gene; Genetic Association

Rationale: Animal models demonstrate that aberrant gene expression in utero can result abnormal pulmonary phenotypes.Objectives: We sought to identify genes are differentially expressed during airway development and test the hypothesis variants these influence lung function patients with asthma.Methods: Stage 1 (Gene Expression): Differential analysis across pseudoglandular (n = 27) canalicular 9) stages of human was performed using regularized t tests multiple comparison adjustments. 2 (Genetic Association): Genetic association analyses (FEV1, FVC, FEV1/FVC) for five were conducted 403 parent-child trios from Childhood Asthma Management Program (CAMP). Associations replicated 583 Genetics Costa Rica study.Measurements Main Results: Of 1,776 between (gestational age: 7–16 wk) 17–26 stages, we selected 5 Wnt pathway testing. Thirteen single nucleotide polymorphisms three demonstrated CAMP (P < 0.05), associations two Ricans: Wnt1-inducible signaling protein FEV1 (combined P 0.0005) FVC 0.0004), inhibitory factor 0.003) FEV1/FVC 0.003).Conclusions: associated impaired childhood asthma cohorts. Furthermore, profiling fetal be used implicated pathogenesis impairment individuals asthma.