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Organic cation transporter variation and response to smoking cessation therapies

Andrew W Bergen1, Harold S Javitz2, Ruth Krasnow2

  • 1Center for Health Sciences, SRI International, Menlo Park, CA; andrew.bergen@sri.com.

Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco
|August 22, 2014
PubMed
Abstract

Insights

Genetic variations in the organic cation transporter 2 (SLC22A2) gene are associated with smoking cessation success. Specific SLC22A2 polymorphisms show a link to abstinence rates, particularly with nicotine replacement therapy and varenicline.

Area of Science:

  • Pharmacogenetics
  • Genetics
  • Clinical Pharmacology

Background:

  • Investigated genetic variations in chr6q25.3 organic cation transporter genes (SLC22A1, SLC22A2, SLC22A3) and their association with smoking cessation therapy response.
  • Organic cation transporters are crucial for various physiological processes and are targets for smoking cessation pharmacotherapies.

Purpose of the Study:

  • To evaluate the association between common polymorphisms in SLC22A2 and smoking cessation treatment outcomes.
  • To identify potential pharmacogenetic markers for predicting smoking cessation success.

Main Methods:

  • Utilized mega-regression analysis on 7 common polymorphisms within SLC22A2.
  • Assessed associations with 7-day point prevalence abstinence in European-ancestry participants across 7 randomized controlled trials.
  • Adjusted for demographic, population genetic, and trial-specific covariates.

Main Results:

  • Two SLC22A2 polymorphisms, rs316019 and rs316006, showed nominally statistically significant associations with smoking abstinence.
  • rs316019 was associated with abstinence in the overall group and specifically in those receiving nicotine replacement therapy (NRT).
  • rs316006 was associated with abstinence in participants treated with varenicline.

Conclusions:

  • The OCT2 Ser270Ala polymorphism (rs316019) demonstrates a statistically significant association with smoking abstinence in European-ancestry individuals.
  • These preliminary findings suggest a pharmacogenetic role for SLC22A2/OCT2 in smoking cessation.
  • Further replication in diverse populations and additional trials is warranted to confirm these results.

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