INTRODUCTION: Genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in the CHRNA5/A3/B4 gene cluster with heaviness of smoking. The nicotine metabolite ratio (NMR), a measure of the rate of nicotine metabolism, is associated with the number of cigarettes per day (CPD) and likelihood of cessation. We tested the potential interacting effects of these two risk factors on CPD. METHODS: Pretreatment data from three prior clinical trials were pooled for analysis. One thousand and thirty treatment seekers of European ancestry with genotype data for the CHRNA5/A3/B4 SNPs rs578776 and rs1051730 and complete data for NMR and CPD at pretreatment were included. Data for the third SNP, rs16969968, were available for 677 individuals. Linear regression models estimated the main and interacting effects of genotype and NMR on CPD. RESULTS: We confirmed independent associations between the NMR and CPD as well as between the SNPs rs16969968 and rs1051730 and CPD. We did not detect a significant interaction between NMR and any of the SNPs examined. CONCLUSIONS: This study demonstrates the additive and independent association of the NMR and SNPs in the CHRNA5/A3/B4 gene cluster with smoking rate in treatment-seeking smokers.
INTRODUCTION: Genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in the CHRNA5/A3/B4 gene cluster with heaviness of smoking. The nicotine metabolite ratio (NMR), a measure of the rate of nicotine metabolism, is associated with the number of cigarettes per day (CPD) and likelihood of cessation. We tested the potential interacting effects of these two risk factors on CPD. METHODS: Pretreatment data from three prior clinical trials were pooled for analysis. One thousand and thirty treatment seekers of European ancestry with genotype data for the CHRNA5/A3/B4 SNPs rs578776 and rs1051730 and complete data for NMR and CPD at pretreatment were included. Data for the third SNP, rs16969968, were available for 677 individuals. Linear regression models estimated the main and interacting effects of genotype and NMR on CPD. RESULTS: We confirmed independent associations between the NMR and CPD as well as between the SNPs rs16969968 and rs1051730 and CPD. We did not detect a significant interaction between NMR and any of the SNPs examined. CONCLUSIONS: This study demonstrates the additive and independent association of the NMR and SNPs in the CHRNA5/A3/B4 gene cluster with smoking rate in treatment-seeking smokers.
Authors: J M Vink; A L Beem; D Posthuma; M C Neale; G Willemsen; K S Kendler; P E Slagboom; D I Boomsma Journal: Pharmacogenomics J Date: 2004 Impact factor: 3.550
Authors: W Berrettini; X Yuan; F Tozzi; K Song; C Francks; H Chilcoat; D Waterworth; P Muglia; V Mooser Journal: Mol Psychiatry Date: 2008-01-29 Impact factor: 15.992
Authors: Laura Jean Bierut; Jerry A Stitzel; Jen C Wang; Anthony L Hinrichs; Richard A Grucza; Xiaoling Xuei; Nancy L Saccone; Scott F Saccone; Sarah Bertelsen; Louis Fox; William J Horton; Naomi Breslau; John Budde; C Robert Cloninger; Danielle M Dick; Tatiana Foroud; Dorothy Hatsukami; Victor Hesselbrock; Eric O Johnson; John Kramer; Samuel Kuperman; Pamela A F Madden; Kevin Mayo; John Nurnberger; Ovide Pomerleau; Bernice Porjesz; Oliver Reyes; Marc Schuckit; Gary Swan; Jay A Tischfield; Howard J Edenberg; John P Rice; Alison M Goate Journal: Am J Psychiatry Date: 2008-06-02 Impact factor: 18.112
Authors: Victoria L Stevens; Laura J Bierut; Jeffrey T Talbot; Jen C Wang; Juzhong Sun; Anthony L Hinrichs; Michael J Thun; Alison Goate; Eugenia E Calle Journal: Cancer Epidemiol Biomarkers Prev Date: 2008-11-24 Impact factor: 4.254
Authors: Robert A Schnoll; Freda Patterson; E Paul Wileyto; Rachel F Tyndale; Neal Benowitz; Caryn Lerman Journal: Pharmacol Biochem Behav Date: 2008-10-31 Impact factor: 3.533
Authors: Bradley N Collins; E Paul Wileyto; Freda Patterson; Margaret Rukstalis; Janet Audrain-McGovern; Vyga Kaufmann; Angela Pinto; Larry Hawk; Raymond Niaura; Leonard H Epstein; Caryn Lerman Journal: Nicotine Tob Res Date: 2004-02 Impact factor: 4.244
Authors: Jaimee L Heffner; Jeffrey R Strawn; Melissa P DelBello; Stephen M Strakowski; Robert M Anthenelli Journal: Bipolar Disord Date: 2011 Aug-Sep Impact factor: 6.744
Authors: Anne Tammimäki; Penelope Herder; Ping Li; Caroline Esch; James R Laughlin; Gustav Akk; Jerry A Stitzel Journal: Neuropharmacology Date: 2012-07-20 Impact factor: 5.250
Authors: Wonho Lee; Riju Ray; Andrew W Bergen; Gary E Swan; Paul Thomas; Rachel F Tyndale; Neal L Benowitz; Caryn Lerman; David V Conti Journal: Pharmacogenet Genomics Date: 2012-07 Impact factor: 2.089
Authors: Meghan J Chenoweth; Maria Novalen; Larry W Hawk; Robert A Schnoll; Tony P George; Paul M Cinciripini; Caryn Lerman; Rachel F Tyndale Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-07-10 Impact factor: 4.254
Authors: Ruth E Krasnow; Lisa M Jack; Christina N Lessov-Schlaggar; Andrew W Bergen; Gary E Swan Journal: Twin Res Hum Genet Date: 2012-10-19 Impact factor: 1.587
Authors: Adam M Leventhal; Wonho Lee; Andrew W Bergen; Gary E Swan; Rachel F Tyndale; Caryn Lerman; David V Conti Journal: Drug Alcohol Depend Date: 2014-03-05 Impact factor: 4.492