Nicotinic acetylcholine receptor variants associated with susceptibility to chronic obstructive pulmonary disease: a meta-analysis

Abstract

Background: Only 10-15% of smokers develop chronic obstructive pulmonary disease (COPD) which indicates genetic susceptibility to the disease. Recent studies suggested an association between COPD and polymorphisms in CHRNA coding subunits of nicotinic acetylcholine receptor. Herein, we performed a meta-analysis to clarify the impact of CHRNA variants on COPD.

Methods: We searched Web of Knowledge and Medline from 1990 through June 2011 for COPD gene studies reporting variants on CHRNA. Pooled odds ratios (ORs) were calculated using the major allele or genotype as reference group.

Results: Among seven reported variants in CHRNA, rs1051730 was finally analyzed with sufficient studies. Totally 3460 COPD and 11437 controls from 7 individual studies were pooled-analyzed. A-allele of rs1051730 was associated with an increased risk of COPD regardless of smoking exposure (pooled OR = 1.26, 95% CI 1.18-1.34, p < 10⁻⁵). At the genotypic level, the ORs gradually increased per A-allele (OR = 1.27 and 1.50 for GA and AA respectively, p < 10⁻⁵). Besides, AA genotype exhibited an association with reduced FEV1% predicted (mean difference 3.51%, 95%CI 0.87-6.16%, p = 0.009) and increased risk of emphysema (OR 1.93, 95%CI 1.29-2.90, p = 0.001).

Conclusions: Our findings suggest that rs1051730 in CHRNA is a susceptibility variant for COPD, in terms of both airway obstruction and parenchyma destruction.

Figure 1

Study selection process. COPD, chronic obstructive pulmonary disease.

Figure 2

Forest plot of the pooled ORs for COPD comparing rs1051730 A-allele with G-allele. The circles in squares and the horizontal lines represent the point estimate and 95% CI, respectively, for each included study; the diamond shape represents the pooled estimate and 95% CI. OR, odds ratio; COPD, chronic obstructive pulmonary disease; CI, confidence interval; df, degree of freedom.

Figure 3

Funnel plot for the assessment of potential publication bias in rs1051730 variant frequencies. SE, standard error; OR, odds ratio; COPD, chronic obstructive pulmonary disease.

Figure 4

Forest plot showing the comparisons of FEV₁%predicted between different rs1051730 genotypes. A: GA versus GG; B. AA versus GG. The circles in squares and the horizontal lines represent the mean difference and 95% CI, respectively, for each included study; the diamond shape represents the pooled mean difference and 95% CI. FEV₁, forced expired volume in 1 second; CI, confidence interval; df, degree of freedom.