A systematic review of genetic variation within nicotinic acetylcholine receptor genes and cigarette smoking cessation

source extracted confidence: high 2026-04-09
#bupropion #genetic-variation #humans #nicotine #polymorphism-single-nucleotide

A systematic review of genetic variation within nicotinic acetylcholine receptor genes and cigarette smoking cessation

Jones et al., 2022 | Drug Alcohol Depend | Systematic Review

Citation

Jones Stephanie K, Wolf Bethany J, ... Alberg Anthony J. A systematic review of genetic variation within nicotinic acetylcholine receptor genes and cigarette smoking cessation. Drug Alcohol Depend. 2022-Oct-01;239:109596. doi:10.1016/j.drugalcdep.2022.109596

Abstract

BACKGROUND: Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting likelihood of smoking cessation. METHODS: A systematic review was conducted summarizing evidence of associations between single nucleotide polymorphisms (SNPs) of nAChR genes and smoking cessation. From 24 articles meeting inclusion criteria, summary odds ratios (ORs) for associations between nine SNPs and smoking cessation were calculated from 26 studies (N = 233-29,072) stratified by gene, ancestry, study design, and pharmacotherapy; SNPs in linkage disequilibrium were pooled. Results for a tenth SNP from two GWAS were summarized. RESULTS: People of European ancestry with minor alleles of CHRNA5 rs16969968 and CHRNA3 rs1051730 had longer time to cessation [HR = 0.90, 95 % CI 0.88 - 0.92 (n = 2 studies)] and lower odds of cessation [OR = 0.88, 95 % CI 0.80 - 0.97 (n = 5 cohort studies), OR = 0.64, 95 % CI 0.45 - 0.90 (n = 4 placebo arms)]. Risk of persistent smoking associated with these alleles was attenuated in smokers receiving nicotine replacement therapy (NRT). Recipients of bupropion alone or with NRT with these alleles had higher, though not statistically significant, odds of cessation. Results for CHRNA5 rs588765 and rs680244 were similar to rs16969968/rs1051730 findings. Evidence was limited for other SNPs. CONCLUSION: Evidence consistently indicates the minor alleles of four SNPs within CHRNA3 or CHRNA5 are risk alleles for cessation failure. Analysis by pharmacotherapy revealed bupropion may be the most efficacious intervention for people with these alleles.

Key Findings

People of European ancestry with minor alleles of CHRNA5 rs16969968 and CHRNA3 rs1051730 had longer time to cessation [HR = 0.90, 95 % CI 0.88 - 0.92 (n = 2 studies)] and lower odds of cessation [OR = 0.88, 95 % CI 0.80 - 0.97 (n = 5 cohort studies), OR = 0.64, 95 % CI 0.45 - 0.90 (n = 4 placebo arms)]. Risk of persistent smoking associated with these alleles was attenuated in smokers receiving nicotine replacement therapy (NRT). Recipients of bupropion alone or with NRT with these alleles had h

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 233
Age Range See abstract
Condition See abstract

MeSH Terms

  • Bupropion
  • Genetic Variation
  • Humans
  • Nicotine
  • Polymorphism, Single Nucleotide
  • Receptors, Nicotinic
  • Smoking Cessation
  • Tobacco Products
  • Tobacco Use Cessation Devices

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review, Research Support, N.I.H., Extramural
  • Vertical: niacin

Provenance

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