Table 1.

Summary of pharmacogenetic effects in nicotine-dependence clinical trials

Genes	Treatment	Gender interaction	Main finding	Citation
Pharmacokinetics/drug metabolizing enzymes
CYP2A6	NRT	Not reported	Genotypes related to 3-HC/cotine ratio; slow metabolizers smoke fewer cigarettes and are less nicotine dependent; in patch condition, slow metabolizers had higher plasma nicotine but equal patch use; in spray condition, fast metabolizers used more spray but had equal plasma nicotine	28
CYP2A6 (3-HC/Cotinine Ratio)	NRT	Not reported	3-HC/cotinine ratio predicted nicotine patch efficacy butnot nasal spray; there was a 30% reduction in chance of cessation following patch therapy with each increasing quartile of metabolite ratio	30
CYP2B6	Bupropion	Yes	Slow metabolizers had increased cravings after quitting and higher relapse rates; bupropion attenuated theses effects among females	74
	Bupropion	No	Among smokers with decreased bupropion metabolism, bupropion produced significantly higher abstinence rates than placebo; bupropion was no more effective than placebo for smokers with normal bupropion metabolism	75
Pharmacodynamics/drug target genes
DRD2 (Taq 1A)	NRT	Yes	Quit rates from patch therapy were higher for women with the Taq1 A1 allele, but there was no genotype effect for men	62
	NRT	No	Quit rates from patch therapy were significantly greater for smokers with the Taq1 A1 allele and the DBH A allele	63
	Bupropion	Yes	Women with the DRD2 A2/A2 allele were more likely to quit smoking, compared to women with A1 alleles	80
	Bupropion	No	Those with DRD2 A2/A2 alleles showed better treatment response, versus those with A1/A1 or A1/A2 alleles	78
	Venlafaxine		Smokers with the DRD2 A1 allele (A1/A1/A2) quit significantly less often than the homozygous A2s	79
DRD2 (-141 Ins/Del)	NRT	No	Smokers homozygous for the Del C allele responded better to NRT than carriers of the Ins C allele	66
	Bupropion	No	Smokers homozygous for the Ins C allele had higher quit rates following bupropion, versus smokers with the Del C allele; smokers with the Del C allele had higher quit rates on placebo	66
	NRT	No	Smokers with at least one copy of the -141 Del allele and two copies of the FREQ rs1054879 A allele were more likely to quit smoking, compared to smokers with other alleles	69
DRD2 (C957T)	NRT	No	Smokers with CT/CC genotypes were less than two-thirds as likely to be abstinent, versus participants with TT genotypes	66
	Bupropion	No	Variants of C957T were not associated with quit rates following bupropion therapy	66
DBH	NRT	No	Smokers with the DBH GA/AA genotype had higher quit rates, compared to those with GG alleles	63
COMT	NRT	Yes	Women with the Met/Met genotype showed higher quit rates following NRT, versus women with the Val/Val allele	53
	Bupropion	No	COMT haplotype from SNPs rs165599 and rs373865 affected response to bupropion, with higher quit rates among smokers carrying the A allele of the rs165599 (A/G) SNP	82
SLC6A3	Bupropion	No	Smokers with DRD2-A2 genotypes and SLC6A3-9 genotypes, versus SLC6A3-10 genotypes, had significantly higher quit rates and a longer latency to relapse	50
	NRT or bupropion	No	Smokers with the 9-repeat allele were more likely to quit smoking following treatment than those with 10/10 repeats	51
	Bupropion	No	There were no main effects for DRD2 and SLC6A3 genotypes on smoking cessation; those with DRD2 A1 and SLC6A3 9-repeat alleles show poorer response to bupropion	49
OPRM1	NRT	Yes	Quit rates following treatment were higher for carriers of the OPRM1 Asp40 variant, versus carriers of the Asn40	54
5-HTTLPR	NRT	No	5-HTTLPR alleles were not related to NRT response	58
	NRT	No	5-HTTLPR alleles were not related to NRT response	57
CHRNA4	NRT	No	Smokers with the TC genotype were more likely to maintain abstinence on nasal spray, but not transdermal patch	71

NRT, nicotine replacement therapy; 3-HC, 3-hydroxycotinin