Title: Variants in the 15q24/25 locus associate with lung function decline in active smokers
Authors: Mohamed Hoesein, Firdaus A A ×
Wauters, Els
Janssens, Wim
Groen, Harry J M
Smolonska, Joanna
Wijmenga, Cisca
Postma, Dirkje S
Boezen, H Marike
De Jong, Pim A
Decramer, Marc
Lammers, Jan-Willem J
Lambrechts, Diether
Zanen, Pieter #
Issue Date: 2013
Publisher: Public Library of Sciene
Series Title: PLoS One vol:8 issue:1 pages:e53219
Article number: 10.1371/journal.pone.0053219
Abstract: Genetic variation in nicotinic acetylcholine receptor subunit genes (nAChRs) is associated with lung function level and chronic obstructive pulmonary disease (COPD). It is unknown whether these variants also predispose to an accelerated lung function decline. We investigated the association of nAChR susceptibility variants with lung function decline and COPD severity. The rs1051730 and rs8034191 variants were genotyped in a population-based cohort of 1,226 heavy smokers (COPACETIC) and in an independent cohort of 883 heavy smokers, of which 653 with COPD of varying severity (LEUVEN). Participants underwent pulmonary function tests at baseline. Lung function decline was assessed over a median follow-up of 3 years in COPACETIC. Current smokers homozygous for the rs1051730 A-allele or rs8034191 G-allele had significantly greater FEV(1)/FVC decline than homozygous carriers of wild-type alleles (3.3% and 4.3%, p = 0.026 and p = 0.009, respectively). In the LEUVEN cohort, rs1051730 AA-carriers and rs8034191 GG-carriers had a two-fold increased risk to suffer from COPD GOLD IV (OR 2.29, 95% confidence interval [CI] = 1.11-4.75; p = 0.025 and OR = 2.42, 95% [CI] = 1.18-4.95; p = 0.016, respectively). The same risk alleles conferred, respectively, a five- and four-fold increased risk to be referred for lung transplantation because of end-stage COPD (OR = 5.0, 95% [CI] = 1.68-14.89; p = 0.004 and OR = 4.06, 95% [CI] = 1.39-11.88; p = 0.010). In Europeans, variants in nAChRs associate with an accelerated lung function decline in current smokers and with clinically relevant COPD.
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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