title: Association of CHRNA5-A3-B4 SNP rs2036527 with smoking cessation therapy response in African-American smokers.
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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A Z X
authors.initials: AZ
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kansas, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Cox
authors.affiliation: 1] Division of General Medical Disciplines, Stanford University School of Medicine, Stanford, California, USA [2] Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, California, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: David
authors.affiliation: Department of Medicine and Center for Health Equity, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Ahluwalia
authors.affiliation: 1] Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, San Francisco, California, USA [2] Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Benowitz
authors.affiliation: 1] Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada [2] Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R F
authors.initials: RF
authors.lastname: Tyndale
mesh_terms: D001741:Black or African American / Q000235:genetics*; D002047:Buprenorphine / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000188:drug therapy / Q000235:genetics*; D016540:Smoking Cessation / Q000379:methods*; D061485:Tobacco Use Cessation Devices; D016896:Treatment Outcome
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D002047:Buprenorphine
references.citation: J Natl Cancer Inst. 2012 Feb 22;104(4):290-8
references.pmid: 22282543
references.citation: Neuropsychopharmacology. 2012 Jun;37(7):1683-8
references.pmid: 22373943
references.citation: J Pharmacol Exp Ther. 2000 Oct;295(1):321-7
references.pmid: 10991997
references.citation: J Natl Cancer Inst. 2012 May 16;104(10):740-8
references.pmid: 22534784
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2010 Apr 5;153B(3):745-56
references.pmid: 19859904
references.citation: Carcinogenesis. 2013 Jan;34(1):93-101
references.pmid: 23027621
references.citation: Genet Epidemiol. 2012 May;36(4):340-51
references.pmid: 22539395
references.citation: Nature. 2008 Apr 3;452(7187):638-642
references.pmid: 18385739
references.citation: Clin Pharmacol Ther. 2009 Jun;85(6):635-43
references.pmid: 19279561
references.citation: N Engl J Med. 2006 Jan 26;354(4):333-42
references.pmid: 16436765
references.citation: Clin Pharmacol Ther. 2012 Dec;92(6):771-7
references.pmid: 23149928
references.citation: Nature. 2011 Mar 31;471(7340):597-601
references.pmid: 21278726
references.citation: J Natl Cancer Inst. 2010 Aug 4;102(15):1199-205
references.pmid: 20554942
references.citation: Am J Psychiatry. 2012 Jul;169(7):735-42
references.pmid: 22648373
references.citation: Nicotine Tob Res. 2003 Apr;5(2):245-54
references.pmid: 12745498
references.citation: Mol Psychiatry. 2012 Sep;17(9):856-66
references.pmid: 21968931
references.citation: Pharmacogenet Genomics. 2013 Feb;23(2):94-103
references.pmid: 23249876
references.citation: J Pharmacol Exp Ther. 1994 Jan;268(1):296-303
references.pmid: 8301571
references.citation: Nat Genet. 2008 May;40(5):616-22
references.pmid: 18385676
references.citation: N Engl J Med. 2010 Jun 17;362(24):2295-303
references.pmid: 20554984
references.citation: J Natl Cancer Inst. 2011 Sep 7;103(17):1342-6
references.pmid: 21747048
references.citation: Arch Gen Psychiatry. 2007 Sep;64(9):1078-86
references.pmid: 17768273
references.citation: Neuropsychopharmacology. 2012 Feb;37(3):641-50
references.pmid: 22048466
references.citation: Neuropsychopharmacology. 2006 Jan;31(1):231-42
references.pmid: 16123753
references.citation: Hum Mol Genet. 2009 Aug 1;18(15):2922-7
references.pmid: 19429911
references.citation: Addiction. 2006 Jun;101(6):883-91
references.pmid: 16696632
references.citation: Nicotine Tob Res. 2011 Sep;13(9):772-83
references.pmid: 21546441
references.citation: PLoS Genet. 2010 Aug 05;6(8):
references.pmid: 20700436
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2011 Apr;156B(3):275-84
references.pmid: 21268243
references.citation: Nicotine Tob Res. 2011 Oct;13(10):982-8
references.pmid: 21690317
references.citation: Nat Genet. 2010 May;42(5):448-53
references.pmid: 20418888
references.citation: Addiction. 2013 Oct;108(10):1818-28
references.pmid: 23692359
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Dec;19(12):3013-9
references.pmid: 20962297
references.citation: Transl Psychiatry. 2012 May 22;2:e119
references.pmid: 22832964
references.citation: Nat Genet. 2010 May;42(5):436-40
references.pmid: 20418889