This study evaluated association between common and rare sequence variants in 10 nicotinic acetylcholine receptor subunit genes and the severity of nausea 21 days after initiating the standard, Food and Drug Administration-approved varenicline regimen for smoking cessation. A total of 397 participants from a randomized clinical effectiveness trial with complete clinical and DNA resequencing data were included in the analysis (mean age=49.2 years; 68.0% female). Evidence for significant association between common sequence variants in CHRNB2 and nausea severity was obtained after adjusting for age, gender and correlated tests (all PACT<0.05). Individuals with the minor allele of CHRNB2 variants experienced less nausea than did those without the minor allele, consistent with previously reported findings for CHRNB2 and the occurrence of nausea and dizziness as a consequence of first smoking attempt in adolescents, and with the known neurophysiology of nausea. As nausea is the most common reason for discontinuance of varenicline, further pharmacogenetic investigations are warranted.
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We thank the participants of the COMPASS smoking cessation clinical trial (CA071358, PI Gary Swan). We also appreciate the efforts of the quit coaches and the research staff of Free & Clear, the staff of the Group Health Research Institute's Survey Research Program, and Mary McElroy, Gaye Courtney, Peggy Giacalone and Trish McLeod of SRI International, whose contributions were essential to provide the data for this analysis. We also acknowledge the consultative assistance of Dr Ray Niaura, Dr Caryn Lerman and Dr Neal Benowitz, who served on the data and safety monitoring board of the study. Dr Lerman and Dr Tyndale read and commented on an earlier version of this article. This study was supported by CA071358 (a grant from NCI), U01DA020830 (a grant from NIDA, NCI, NIGMS and NHGRI), the Material Transfer and Research Agreement between SRI International and Perlegen Sciences, and the National Cancer Institute (grant # R01CA071358). This study is registered at Clinicaltrials.gov (NCT00301145).
Varenicline and the nominal support for recruiting participants was provided by Pfizer. Neither entity had any role in the study design, collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the report for publication. Swan, Javitz, Jack, Wessel, Michel, Hinds, Stokowski, McClure, Catz, Richards, Zbikowski, Deprey, McAfee, Conti and Bergen declare that all financial and material support for this work was provided by their primary employer. Javitz, Jack, Wessel, Michel, Hinds, Stokowski, McClure, Catz, Richards, Zbikowski, Deprey, McAfee and Bergen declare that, except for income provided from their primary employer, no other financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional services nor are there personal financial holdings that could be perceived as constituting a potential conflict of interest. Dr Swan received financial support from Pfizer to attend a 1-day advisory meeting in 2008. Dr Conti was a paid consultant for Pfizer in 2008. Dr Wessel is currently employed by Indiana University, Dr Hinds is currently employed by 23 and Me, Dr Stokowski is currently employed by Tandem Diagnostics and Dr McAfee is currently employed by the Centers for Disease Control and Prevention.
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Swan, G., Javitz, H., Jack, L. et al. Varenicline for smoking cessation: nausea severity and variation in nicotinic receptor genes. Pharmacogenomics J 12, 349–358 (2012). https://doi.org/10.1038/tpj.2011.19