Organic cation transporter variation and response to smoking cessation therapies.

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Bergen AW, Javitz HS, Krasnow R, Michel M, Nishita D, Conti DV, Edlund CK, Kwok PY, McClure JB, Kim RB, Hall SM, Tyndale RF, Baker TB, Benowitz NL, Swan GE

Organic cation transporter variation and response to smoking cessation therapies.

Nicotine Tob Res. 2014 Dec;16(12):1638-46. doi: 10.1093/ntr/ntu161. Epub 2014 Aug 20.

PubMed ID

25143296 [ View in PubMed

]

Abstract

INTRODUCTION: We evaluated chr6q25.3 organic cation transporter gene (SLC22A1, SLC22A2, SLC22A3) variation and response to smoking cessation therapies. The corresponding proteins are low-affinity transporters of choline, acetylcholine and monoamines, and smoking cessation pharmacotherapies expressed in multiple tissues. METHODS: We selected 7 common polymorphisms for mega-regression analysis. We assessed additive model association of polymorphisms with 7-day point prevalence abstinence overall and by assigned pharmacotherapy at end of treatment and at 6 months among European-ancestry participants of 7 randomized controlled trials adjusted for demographic, population genetic, and trial covariates. RESULTS: Initial results were obtained in 6 trials with 1,839 participants. Nominally statistically significant associations of 2 SLC22A2 polymorphisms were observed: (1) with rs316019 at 6 months, overall ([c.808T>G; p.Ser270Ala], OR = 1.306, 95% CI = 1.034-1.649, p = .025), and among those randomized to nicotine replacement therapy (NRT) (OR = 1.784, 95% CI = 1.072-2.970, p = .026); and (2) with rs316006 (c.1502-529A>T) among those randomized to varenicline (OR = 1.420, 95% CI = 1.038-1.944, p = .028, OR = 1.362, 95% CI = 1.001-1.853, p = .04) at end of treatment and 6 months. Individuals randomized to NRT from a seventh trial were genotyped for rs316019; rs316019 was associated with a nominally statistically significant effect on abstinence overall at 6 months among 2,233 participants (OR = 1.249, 95% CI = 1.007-1.550, p = .043). CONCLUSIONS: The functional OCT2 Ser270Ala polymorphism is nominally statistically significantly associated with abstinence among European-ancestry treatment-seeking smokers after adjustments for pharmacotherapy, demographics, population genetics, and without adjustment for multiple testing of 7 SNPs. Replication of these preliminary findings in additional randomized controlled trials of smoking cessation therapies and from multiple continental populations would describe another pharmacogenetic role for SLC22A2/OCT2.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Bupropion	Solute carrier family 22 member 2	Protein	Humans	Unknown	Inhibitor	Details
Varenicline	Solute carrier family 22 member 2	Protein	Humans	Unknown	Substrate Inhibitor	Details

Drug Interactions

Drugs	Interaction
Integrate drug-drug interactions in your software
Amantadine Bupropion	The excretion of Amantadine can be decreased when combined with Bupropion.
Choline Bupropion	The excretion of Choline can be decreased when combined with Bupropion.
Choline salicylate Bupropion	The excretion of Choline salicylate can be decreased when combined with Bupropion.
Cisplatin Bupropion	The excretion of Cisplatin can be decreased when combined with Bupropion.
Dalfampridine Bupropion	The excretion of Dalfampridine can be decreased when combined with Bupropion.