Nicotinic acetylcholine receptor variants are related to smoking habits, but not directly to COPD

Abstract

Genome-wide association studies identified single nucleotide polymorphisms (SNPs) in the nicotinic acetylcholine receptors (nAChRs) cluster as a risk factor for nicotine dependency and COPD. We investigated whether SNPs in the nAChR cluster are associated with smoking habits and lung function decline, and if these potential associations are independent of each other. The SNPs rs569207, rs1051730 and rs8034191 in the nAChR cluster were analyzed in the Vlagtwedde-Vlaardingen cohort (n = 1,390) that was followed for 25 years. We used GEE and LME models to analyze the associations of the SNPs with quitting or restarting smoking and with the annual FEV(1) decline respectively. Individuals homozygote (CC) for rs569207 were more likely to quit smoking (OR (95%CI) = 1.58 (1.05-2.38)) compared to wild-type (TT) individuals. Individuals homozygote (TT) for rs1051730 were less likely to quit smoking (0.64 (0.42; 0.97)) compared to wild-type (CC) individuals. None of the SNPs was significantly associated with the annual FEV(1) decline in smokers and ex-smokers. We show that SNPs in the nAChR region are associated with smoking habits such as quitting smoking, but have no significant effect on the annual FEV(1) decline in smokers and ex-smokers, suggesting a potential role of these SNPs in COPD development via smoking habits rather than via direct effects on lung function.

Figure 1. SNPs in the nAChR cluster and OR (95%CI) for quitting smoking in subjects who smoke (upper graph), and OR (95%CI) for restarting to smoke in ex-smokers (lower graph).

Nr. of pairs = number of paired observations in which the subject stopped respectively restarted smoking/ total number of paired observations included in the analysis; Circles represent the odd ratio (OR) and vertical bars represent 95% confidence interval (CI); Wild type was set to one as the reference category; Different total number of paired observations for the SNP genotypes are due to missing data on genotype or smoking habits. The analyses are adjusted for gender and the time between 2 successive surveys. rs569207 TT = wild-type, TC = heterozygote, CC = homozygote variant rs1051730 CC = wild-type CT = heterozygote TT = homozygote variant rs8034191 GG = wild-type, GA = heterozygote, AA = homozygote variant.

Figure 2. Summary of the observed associations in the current study.

SNPs = single nucleotide polymorphisms; COPD = Chronic Obstructive Pulmonary Disease; nAChR = nicotinic acetylcholine receptor; + = association; − = no association.