Showing papers by "Nancy L. Saccone published in 2014"
TL;DR: Nicotine replacement therapy is effective among individuals with fast, but not slow, CYP2A6-defined nicotine metabolism, and the effect of bupropion on relapse likelihood is unlikely to be affected by nicotine metabolism as estimated from CYP1A6 genotype.
Abstract: Background and aims
Evidence suggests that both the nicotinic receptor α5 subunit (CHRNA5) and Cytochrome P450 2A6 (CYP2A6) genotypes influence smoking cessation success and response to pharmacotherapy. We examine the effect of CYP2A6 genotype on smoking cessation success and response to cessation pharmacotherapy, and combine these effects with those of CHRNA5 genotypes.
88 citations
TL;DR: Exhaled CO, a biomarker that is simple to measure, captures aspects of cigarette smoke exposure in current smokers beyond the number of cigarettes smoked per day, suggesting that genetic associations with COPD or lung cancer that persist after adjusting for self-reported smoking behavior may still reflect genetic effects on smoking exposure.
Abstract: Rationale: The CHRNA5-CHRNA3-CHRNB4 locus is associated with self-reported smoking behavior and also harbors the strongest genetic associations with chronic obstructive pulmonary disease (COPD) and lung cancer. Because the associations with lung disease remain after adjustment for self-reported smoking behaviors, it has been asserted that CHRNA5-CHRNA3-CHRNB4 variants increase COPD and lung cancer susceptibility independently of their effects on smoking.
Objectives: To compare the genetic associations of exhaled carbon monoxide (CO), a biomarker of current cigarette exposure, with self-reported smoking behaviors.
Methods: A total of 1,521 European American and 247 African American current smokers recruited into smoking cessation studies were assessed for CO at intake before smoking cessation. DNA samples were genotyped using the Illumina Omni2.5 microarray. Genetic associations with CO and smoking behaviors (cigarettes smoked per day, Fagerstrom test for nicotine dependence) were studied.
Measurements and Main Results: Variants in the CHRNA5-CHRNA3-CHRNB4 locus, including rs16969968, a nonsynonymous variant in CHRNA5, are genomewide association study–significantly associated with CO (β = 2.66; 95% confidence interval [CI], 1.74–3.58; P = 1.65 × 10−8), and this association remains strong after adjusting for smoking behavior (β = 2.18; 95% CI, 1.32–3.04; P = 7.47 × 10−7). The correlation between CO and cigarettes per day is statistically significantly lower (z = 3.43; P = 6.07 × 10−4) in African Americans (r = 0.14; 95% CI, 0.02–0.26; P = 0.003) than in European-Americans (r = 0.36; 95% CI, 0.31–0.40; P = 0.0001).
Conclusions: Exhaled CO, a biomarker that is simple to measure, captures aspects of cigarette smoke exposure in current smokers beyond the number of cigarettes smoked per day. Behavioral measures of smoking are therefore insufficient indices of cigarette smoke exposure, suggesting that genetic associations with COPD or lung cancer that persist after adjusting for self-reported smoking behavior may still reflect genetic effects on smoking exposure.
40 citations
TL;DR: Improved understanding of the mechanisms underlying smoking behavior and smoking cessation must be a high public health priority so the authors can best intervene at both the public health level and the individual level.
38 citations
TL;DR: The common variant rs13273442 in the CHRNB3-CHNRA6 region is associated significantly with nicotine dependence in European Americans and African Americans across studies recruited for nicotine, alcohol and cocaine dependence.
Abstract: Aims Studies have shown association between common variants in the α6-β3 nicotinic receptor subunit gene cluster and nicotine dependence in European ancestry populations. We investigate whether this generalizes to African Americans, whether the association is specific to nicotine dependence and whether this region contains additional genetic contributors to nicotine dependence. Design We examined consistency of association across studies and race between the α6β3 nicotinic receptor subunit locus and nicotine, alcohol, marijuana and cocaine dependence in three independent studies. Setting United States of America. Participants European Americans and African Americans from three case-control studies of substance dependence. Measurements Subjects were evaluated using the Semi- Structured Assessment for the Genetics of Alcoholism. Nicotine dependence was determined using the Fagerstrom Test for Nicotine Dependence. Findings The single nucleotide polymorphism rs13273442 was associated significantly with nicotine dependence across all three studies in both ancestry groups (odds ratio (OR) = 0.75, P = 5.8 × 10 −4 European Americans; OR = 0.80, P = 0.05 African Americans). No other substance dependence was associated con- sistently with this variant in either group. Another SNP in the region, rs4952, remains modestly associated with nicotine dependence in the combined data after conditioning on rs13273442. Conclusions The common variant rs13273442 in the CHRNB3-CHNRA6 region is associated significantly with nicotine dependence in European Americans and African Americans across studies recruited for nicotine, alcohol and cocaine dependence. Although these data are modestly powered for other substances, our results provide no evidence that correlates of rs13273442 represent a general substance dependence liability. Additional variants probably account for some of the association of this region to nicotine dependence.
33 citations