How to Cite this Article: Sarginson JE, Killen JD, Lazzeroni LC, Fortmann SP, Ryan HS, Schatzberg AF, Murphy GM. 2011. Markers in the 15q24 Nicotinic Receptor Subunit Gene Cluster (CHRNA5-A3-B4) Predict Severity of Nicotine Addiction and Response to Smoking Cessation Therapy. Am J Med Genet Part B 156:275–284.
Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine addiction and response to smoking cessation therapy†
Article first published online: 25 JAN 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 156, Issue 3, pages 275–284, April 2011
How to Cite
Sarginson, J. E., Killen, J. D., Lazzeroni, L. C., Fortmann, S. P., Ryan, H. S., Schatzberg, A. F. and Murphy, G. M. (2011), Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine addiction and response to smoking cessation therapy. Am. J. Med. Genet., 156: 275–284. doi: 10.1002/ajmg.b.31155
- Issue published online: 11 MAR 2011
- Article first published online: 25 JAN 2011
- Manuscript Accepted: 17 NOV 2010
- Manuscript Received: 16 JUN 2010
- NIH. Grant Number: CA90300 DA017441 DA017457
- California Tobacco-Related Diseases Research Program
- Department of Veterans Affairs
- nicotinic receptors;
- transdermal nicotine
Stopping smoking is difficult even with treatment. Many patients prescribed pharmacologic treatments for smoking cessation experience side effects or lack of efficacy. We performed a pharmacogenetic study of the efficacy and tolerability of bupropion and transdermal nicotine (TN), two treatments for smoking cessation. Samples were drawn from two studies. In the first study (Maintenance 1, MT1), 301 smokers received bupropion plus TN for 11 weeks, followed by 14 weeks of placebo or bupropion. In the second study (MT2), 276 smokers received bupropion and TN for 8 weeks. We focused on eight SNPs in the 15q24 region, which contains the genes for the nicotinic cholinergic receptor subunits CHRNA5, CHRNA3, and CHRNB4, and has previously been implicated in nicotine addiction and smoking cessation. Analyses of baseline smoking quantity (SQ) identified an association between SQ and both the functional CHRNA5 SNP rs16969968 (D398N) and the CHRNA3 SNP rs1051730 (Y215Y) in a combined cohort containing MT1 and MT2. An association between SQ and ethnicity was also identified in the combined cohort. Pharmacogenetic analysis showed a significant association between rs8192475 (R37H) in CHRNA3 and both higher craving after quitting and increased withdrawal symptoms over time in MT2. Two markers for point prevalence abstinence, CHRNA5 SNP rs680244 and CHRNB4 SNP rs12914008, were also identified in MT2, with the strongest findings at week 52. These results provide further support for the role of the CHRNA5/A3/B4 subunits in determining number of cigarettes smoked and response to smoking cessation therapy. © 2011 Wiley-Liss, Inc.