Four SNPs in the CHRNA3/5 alpha-neuronal nicotinic acetylcholine receptor subunit locus are associated with COPD risk based on meta-analyses

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#case-control-studies #gene-frequency #genetic-association-studies #genetic-loci #genetic-predisposition-to-disease

Four SNPs in the CHRNA3/5 alpha-neuronal nicotinic acetylcholine receptor subunit locus are associated with COPD risk based on meta-analyses

Cui et al., 2014 | PLoS One | Meta Analysis

Citation

Cui Kai, Ge Xiaoyan, Ma Honglin. Four SNPs in the CHRNA3/5 alpha-neuronal nicotinic acetylcholine receptor subunit locus are associated with COPD risk based on meta-analyses. PLoS One. 2014;9(7):e102324. doi:10.1371/journal.pone.0102324

Abstract

BACKGROUND: Several single nucleotide polymorphisms (SNPs) in an α-neuronal nicotinic acetylcholine receptor subunit (CHRNA3/5) were identified to be associated with chronic obstructive pulmonary disease (COPD) in a study based on a Norwegian population. However, results from subsequent studies have been controversial, particularly in studies recruiting Asians. In the present study, we conducted a comprehensive search and meta-analyses to identify susceptibility SNPs for COPD in the CHRNA3/5 locus. METHODS: A comprehensive literature search was conducted to find studies that have reported an association between SNPs in the CHRNA3/5 locus and COPD risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for each SNP were calculated with the major allele or genotype as the reference group. The influence of individual studies on pooled measures was assessed, in addition to publication bias. RESULTS: A total of 12 articles with 14 eligible studies were included in this analysis. Association between 4 SNPs in the CHRNA3/5 locus and COPD was evaluated and included rs1051730, rs8034191, rs6495309, and rs16969968. Significant associations between the 4 SNPs and COPD were identified under allele (rs1051730: OR = 1.14, 95%CI = 1.10-1.18; rs8034191: OR = 1.29, 95%CI = 1.18-1.41; rs6495309: OR = 1.26, 95%CI = 1.09-1.45; rs16969968: OR = 1.27, 95%CI = 1.17-1.39) and genotype models. Subgroup analysis conducted for rs1051730 showed a significant association between this SNP and COPD risk in non-Asians (OR = 1.14, 95%CI = 1.10-1.18), but not Asians (OR = 1.23, 95%CI = 0.91-1.67). Rs1051730 and rs6495309 were also significantly associated with COPD after adjusting for multiple variables, including age and smoking status. CONCLUSION: Our results indicate that 4 SNPs in the CHRNA3/5 locus are associated with COPD risk. Rs1051730 was particularly associated with COPD in non-Asians, but its role in Asians still needs to be verified. Additional studies will be necessary to assess the effect of rs6495309 on COPD. Although rs1051730 and rs6495309 were shown to be independent risk factors for COPD, validation studies should be performed.

Key Findings

A total of 12 articles with 14 eligible studies were included in this analysis. Association between 4 SNPs in the CHRNA3/5 locus and COPD was evaluated and included rs1051730, rs8034191, rs6495309, and rs16969968. Significant associations between the 4 SNPs and COPD were identified under allele (rs1051730: OR = 1.14, 95%CI = 1.10-1.18; rs8034191: OR = 1.29, 95%CI = 1.18-1.41; rs6495309: OR = 1.26, 95%CI = 1.09-1.45; rs16969968: OR = 1.27, 95%CI = 1.17-1.39) and genotype models. Subgroup analysis

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Case-Control Studies
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Humans
  • Nerve Tissue Proteins
  • Polymorphism, Single Nucleotide
  • Protein Subunits
  • Pulmonary Disease, Chronic Obstructive
  • Receptors, Nicotinic
  • Risk Factors

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis
  • Vertical: niacin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09