Interaction between the DNAH9 gene and early smoke exposure in bronchial hyperresponsiveness

摘要: A previous genome-wide linkage scan of bronchial hyperresponsiveness (BHR) in the French Epidemiological study on Genetics and Environment Asthma (EGEA) families, performed presence a gene×early-life environmental tobacco smoke (ETS) exposure interaction, showed strongest interaction 17p11 region where was detected only among unexposed siblings. Our goal to conduct fine-scale mapping identify single nucleotide polymorphisms (SNPs) interacting with ETS that influence BHR.Analyses were 388 EGEA asthmatic using two-step strategy: 1) selection SNPs displaying family-based association test (FBAT) signals (p≤0.01) BHR siblings, 2) FBAT homogeneity between exposed siblings plus robust log-linear test.A SNP reached threshold (p≤3×10(-3)) for significant both tests, after accounting multiple testing. Results replicated 253 French-Canadian but not 341 UK probably due part differences phenotypic features datasets.The showing belongs toDNAH9(dynein, axonemal, heavy chain 9), promising candidate gene involved respiratory cilia mobility associated primary ciliary dyskinesia, disease abnormalities pulmonary function.