Clinical Pharmacology & Therapeutics - Abstract of article: Association of CHRNA5-A3-B4 SNP rs2036527 With Smoking Cessation Therapy Response in African-American Smokers

Clinical Pharmacology & Therapeutics - Abstract of article: Association of CHRNA5-A3-B4 SNP rs2036527 With Smoking Cessation Therapy Response in African-American Smokers

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Clinical Pharmacology & Therapeutics advance online publication 4 June 2014; doi: 10.1038/clpt.2014.88

Association of CHRNA5-A3-B4 SNP rs2036527 With Smoking Cessation Therapy Response in African-American Smokers

A Z X Zhu¹, Q Zhou¹, L S Cox², S P David^3,4, J S Ahluwalia⁵, N L Benowitz^6,7 and R F Tyndale^1,8

1. ¹Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
2. ²Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kansas, USA
3. ³Division of General Medical Disciplines, Stanford University School of Medicine, Stanford, California, USA
4. ⁴Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, California, USA
5. ⁵Department of Medicine and Center for Health Equity, University of Minnesota Medical School, Minneapolis, Minnesota, USA
6. ⁶Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, San Francisco, California, USA
7. ⁷Department of Medicine, University of California, San Francisco, San Francisco, California, USA
8. ⁸Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

Correspondence: R F Tyndale, (r.tyndale@utoronto.ca)

Received 25 November 2013; Accepted 3 April 2014
Accepted article preview online 14 April 2014; Advance online publication 4 June 2014

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Abstract

Associations between CHRNA5-A3-B4 variants and smoking behaviors exist; however, the association with smoking abstinence is less understood, particularly that among African Americans. In 1,295 African Americans enrolled in two clinical trials, we investigated the association between CHRNA5-A3-B4 and smoking abstinence. The rs2056527(A) allele was associated with lower abstinence with active pharmacotherapy (during treatment: odds ratio (OR) = 0.42, P < 0.001; end of treatment (EOT): OR = 0.55, P = 0.004), or with nicotine gum alone (during treatment: OR = 0.31,P < 0.001; EOT: OR = 0.51, P = 0.02), but not significantly with bupropion, although similar directions and magnitudes were observed (during treatment: OR = 0.54, P = 0.05; EOT: OR = 0.59, P = 0.08). In addition, the rs588765(T) allele was associated with abstinence with gum during treatment (OR = 2.31, P < 0.01). The SNP rs16969968 occurred at a low frequency and was not consistently associated with abstinence. CHRNA5-A3-B4 variants were not associated with tobacco consumption, and adjustments for smoking behaviors did not alter the associations with smoking abstinence. Together, our data suggest that among African Americans, CHRNA5-A3-B4 variants are not associated with baseline smoking but can influence smoking abstinence during active pharmacotherapy.