Single Nucleotide Polymorphisms Within DRD2, COMT, and DBH and Smoking Cessation: A Systematic Review Considering Genetic Differences by Ancestry and Biological Sex.

PURPOSE OF REVIEW: This systematic review summarizes evidence of single nucleotide polymorphism (SNPs) associations with smoking cessation focusing on dopamine receptor or dopamine metabolism genes. Summary odds ratios (ORs) of SNP associations were calculated and stratified by ancestry, pharmacotherapy, and sex where feasible.

RECENT FINDINGS: The 30 included articles reported the results of 32 studies. The minor allele of DRD2/ANKK1 SNP rs1800497 was associated with lower odds of cessation among people of European ancestry [OR = 0.88, 95% CI 0.82 - 0.95, n= 16 studies]; this association was not observed among people of non-European ancestry. Heterogeneity by sex in rs1800497 associations was present [female: OR = 0.91, 95% CI 0.85 - 0.97, n = 9 studies; male: OR = 1.16, 95% CI 0.85 - 1.55, n = 7 studies]. Recipients of nicotine replacement therapy (NRT) with the minor allele of DRD2 SNP rs6277 [OR = 1.43, 95% CI 1.06 - 1.92, n = 2 studies] or COMT SNP rs4680 [OR = 1.61, 95% CI 1.11 - 2.35, n = 3 studies] had increased odds of cessation. Heterogeneity by sex in rs4680 associations was observed [combined sex: OR = 0.73, 95% CI 0.57 - 0.93, n = 3 studies; male: OR = 0.74, 95% CI 0.53 - 1.02, n = 1 study; female: OR = 1.01, 95% CI 0.77 - 1.32, n = 5 studies].

SUMMARY: Associations between rs1800497 and rs4680 and cessation may differ by biological sex. Limited evidence suggests some genetic associations may differ by ancestry and that rs4680 or rs6277 genotype may influence NRT efficacy.