Dataset Information

The relationship between the nicotine metabolite ratio and three self-report measures of nicotine dependence across sex and race.

ABSTRACT:

Rationale

Variability in the rate of nicotine metabolism, measured by the nicotine metabolite ratio (NMR), is associated with smoking behavior. However, data linking the NMR with nicotine dependence measured by the Fagerström test for nicotine dependence (FTND) are mixed. Few past studies have examined alternative measures of nicotine dependence and how this relationship may vary by sex and race.

Objective

Using data from smokers undergoing eligibility evaluation for a smoking cessation clinical trial (n = 833), this study examined variability in the relationship between NMR and nicotine dependence across sex and race and using three measures of nicotine dependence: FTND, time-to-first-cigarette (TTFC), and the heaviness of smoking index (HSI).

Results

Controlling for sex and race, nicotine metabolism was associated with nicotine dependence only when using the HSI (p < 0.05). Male normal metabolizers of nicotine were more likely to have high nicotine dependence based on the FTND and HSI (p < 0.05), but NMR was not related to measures of nicotine dependence in women. For African Americans, the NMR was associated with nicotine dependence only for the TTFC (p < 0.05), but NMR was not associated with nicotine dependence among Caucasians. Post hoc analyses indicated that the NMR was associated with cigarettes per day, overall, and among men and Caucasians (p < 0.05).

Conclusions

While there was some variation in the relationship between nicotine metabolism and nicotine dependence across measures and sex and race, the results indicate that this relationship may be more attributable to the association between NMR and cigarettes per day.

SUBMITTER: Schnoll RA

PROVIDER: S-EPMC4040302 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The relationship between the nicotine metabolite ratio and three self-report measures of nicotine dependence across sex and race.

Schnoll Robert A RA George Tony P TP Hawk Larry L Cinciripini Paul P Wileyto Paul P Tyndale Rachel F RF

Psychopharmacology 20140109 12

<h4>Rationale</h4>Variability in the rate of nicotine metabolism, measured by the nicotine metabolite ratio (NMR), is associated with smoking behavior. However, data linking the NMR with nicotine dependence measured by the Fagerström test for nicotine dependence (FTND) are mixed. Few past studies have examined alternative measures of nicotine dependence and how this relationship may vary by sex and race.<h4>Objective</h4>Using data from smokers undergoing eligibility evaluation for a smoking ces ...[more]

PMID: 24402139

Similar Datasets

Project description:IntroductionMetabolic enzyme variation and other patient and environmental characteristics influence smoking behaviors, treatment success, and risk of related disease. Population-specific variation in metabolic genes contributes to challenges in developing and optimizing pharmacogenetic interventions. We applied a custom genome-wide genotyping array for addiction research (Smokescreen), to three laboratory-based studies of nicotine metabolism with oral or venous administration of labeled nicotine and cotinine, to model nicotine metabolism in multiple populations. The trans-3'-hydroxycotinine/cotinine ratio, the nicotine metabolite ratio (NMR), was the nicotine metabolism measure analyzed.MethodsThree hundred twelve individuals of self-identified European, African, and Asian American ancestry were genotyped and included in ancestry-specific genome-wide association scans (GWAS) and a meta-GWAS analysis of the NMR. We modeled natural-log transformed NMR with covariates: principal components of genetic ancestry, age, sex, body mass index, and smoking status.ResultsAfrican and Asian American NMRs were statistically significantly (P values ≤ 5E-5) lower than European American NMRs. Meta-GWAS analysis identified 36 genome-wide significant variants over a 43 kilobase pair region at CYP2A6 with minimum P = 2.46E-18 at rs12459249, proximal to CYP2A6. Additional minima were located in intron 4 (rs56113850, P = 6.61E-18) and in the CYP2A6-CYP2A7 intergenic region (rs34226463, P = 1.45E-12). Most (34/36) genome-wide significant variants suggested reduced CYP2A6 activity; functional mechanisms were identified and tested in knowledge-bases. Conditional analysis resulted in intergenic variants of possible interest (P values < 5E-5).ConclusionsThis meta-GWAS of the NMR identifies CYP2A6 variants, replicates the top-ranked single nucleotide polymorphism from a recent Finnish meta-GWAS of the NMR, identifies functional mechanisms, and provides pan-continental population biomarkers for nicotine metabolism.ImplicationsThis multiple ancestry meta-GWAS of the laboratory study-based NMR provides novel evidence and replication for genome-wide association of CYP2A6 single nucleotide and insertion-deletion polymorphisms. We identify three regions of genome-wide significance: proximal, intronic, and distal to CYP2A6. We replicate the top-ranking single nucleotide polymorphism from a recent GWAS of the NMR in Finnish smokers, identify a functional mechanism for this intronic variant from in silico analyses of RNA-seq data that is consistent with CYP2A6 expression measured in postmortem lung and liver, and provide additional support for the intergenic region between CYP2A6 and CYP2A7.

Dataset Information

The relationship between the nicotine metabolite ratio and three self-report measures of nicotine dependence across sex and race.

Rationale

Objective

Results

Conclusions

Publications

The relationship between the nicotine metabolite ratio and three self-report measures of nicotine dependence across sex and race.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets