Nicotine Metabolism and Intake in Black and White Smokers

Pérez‐Stable, Eliseo J.

doi:10.1001/jama.280.2.152

Cited by 566 publications

(461 citation statements)

References 26 publications

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“…Alternative explanations for racial disparities in smoking cessation have been suggested and include slower metabolism of nicotine among Black smokers ( Benowitz, O. F. Pomerleau, C. S. Pomerleau, & Jacob, 2003 ;Kandel, Hu, Schaffran, Udry, & Benowitz, 2007 ;Pérez-Stable, Herrera, Jacob, & Benowitz, 1998 ) and higher exposure to CO and other smoke constituents ( Ahijevych & Parsley, 1999 ;Ahijevych et al, 2004 ;Melikian et al, 2007 ). In the present study, we can only speculate that these factors may have contributed to the differential smoking cessation rates demonstrated between White and Black smokers.…”

Section: Discussionmentioning

confidence: 57%

Differential success rates in racial groups: Results of a clinical trial of smoking cessation among female prisoners

Cropsey

Weaver

Eldridge

et al. 2009

Nicotine &Amp; Tobacco Research

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Section: Discussionmentioning

confidence: 57%

Differential success rates in racial groups: Results of a clinical trial of smoking cessation among female prisoners

Cropsey

Weaver

Eldridge

et al. 2009

Nicotine &Amp; Tobacco Research

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“…Compared to Caucasians, individuals of Black-African descent have a significantly reduced fractional conversion of nicotine to cotinine, reduced metabolic clearance of nicotine to cotinine and higher plasma levels of cotinine for similar cigarette consumption [11,12]. Together, this suggests reduced nicotine and cotinine metabolism, likely as a result of genetic variations in CYP2A6.…”

Section: Introductionmentioning

confidence: 99%

A novel CYP2A6 allele, CYP2A6*23, impairs enzyme function in vitro and in vivo and decreases smoking in a population of Black-African descent

Mwenifumbo

Zhao

et al. 2008

Pharmacogenetics and Genomics

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Objectives-CYP2A6 is the main enzyme involved in nicotine metabolism in humans. We have identified a novel allele, CYP2A6*23 (2161C>T, R203C), in individuals of Black-African descent and investigated its impact on enzyme activity and association with smoking status.Methods-Wildtype and variant enzymes containing amino acid changes R203C (CYP2A6*23), R203S (CYP2A6*16) and V365M (CYP2A6*17) were expressed in Escherichia coli. The effect of CYP2A6*23 in vivo was examined in individuals of Black-African descent given 4 mg oral nicotine.Results-CYP2A6*23 occurred at an allele frequency of 2.0% in individuals of Black-African descent (N = 560 alleles, 95% confidence interval 0.8%-3.1%) and was not detected in Caucasians (N = 334 alleles), Chinese (N = 288 alleles) or Japanese (N = 104 alleles). In vitro, CYP2A6.23 had greatly reduced activity towards nicotine C-oxidation similar to CYP2A6.17, as well as reduced coumarin 7-hydroxylation. Conversely, CYP2A6.16 did not differ in activity compared to the wildtype enzyme. The trans-3′-hydroxycotinine to cotinine ratio, a phenotypic measure of CYP2A6 activity in vivo, was lower in CYP2A6*1/*23 and CYP2A6*23/*23 individuals(mean adjusted ratio of 0.60, n = 5) compared to CYP2A6*1/*1 individuals (mean adjusted ratio of 1.21, n = 150) (p < 0.04). CYP2A6*23 trended towards a higher allele frequency in nonsmokers (3.1%, N = 9/286 alleles) compared to smokers (0.7%, N = 2/274 alleles) (p = 0.06).Conclusions-These results suggest the novel CYP2A6*23 allele impairs enzyme function in vitro and in vivo and trends toward an association with lower risk of smoking.

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“…22 In this study, 11 SNPs within SHC3, as well as the haplotypes of various combinations of these SNPs, were analyzed for associations with three adjusted ND measures in 602 nuclear families of either AA or EA origin. In light of the ethnic-specific characteristics of the SNPs among different ethnic groups 29,38 as well as known ethnic differences in ND and nicotine metabolism, 39,40 we not only performed association analysis on the combined sample (to increase power) but also on ethnicity-specific samples separately. We identified two major haplotypes, A-C-T-A-T-A at a frequency of 27.8 and 17.6%, respectively, and C-T-A-G-T at 44.7 and 30.6%, respectively, in the AA and combined samples.…”

Section: Discussionmentioning

confidence: 99%

Linkage and association studies in African- and Caucasian-American populations demonstrate that SHC3 is a novel susceptibility locus for nicotine dependence

Sun

Lou

et al. 2006

Mol Psychiatry

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Our previous linkage study demonstrated that the 9q22-q23 chromosome region showed a 'suggestive' linkage to nicotine dependence (ND) in the Framingham Heart Study population. In this study, we provide further evidence for the linkage of this region to ND in an independent sample. Within this region, the gene encoding Src homology 2 domain-containing transforming protein C3 (SHC3) represents a plausible candidate for association with ND, assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerströ m Test for ND (FTND). We utilized 11 single-nucleotide polymorphisms within SHC3 to examine the association with ND in 602 nuclear families of either African-American (AA) or EuropeanAmerican (EA) origin. Individual SNP-based analysis indicated three SNPs for AAs and one for EAs were significantly associated with at least one ND measure. Haplotype analysis revealed that the haplotypes A-C-T-A-T-A of rs12519-rs3750399-rs4877042-rs2297313-rs1547696-rs1331188, with a frequency of 27.8 and 17.6%, and C-T-A-G-T of rs3750399-rs4877042-rs2297313-rs3818668-rs1547696, at a frequency of 44.7 and 30.6% in the AA and Combined samples, respectively, were significantly inversely associated with the ND measures. In the EA sample, another haplotype with a frequency of 10.6%, A-G-T-G of rs1331188-rs1556384-rs4534195-rs1411836, showed a significant inverse association with ND measures. These associations remained significant after Bonferroni correction. We further demonstrated the SHC3 contributed 40.1-59.2% (depending on the ND measures) of the linkage signals detected on chromosome 9. As further support, we found that nicotine administered through infusion increased the Shc3 mRNA level by 60% in the rat striatum, and decreased it by 22% in the nucleus accumbens (NA). At the protein level, Shc3 was decreased by 38.0% in the NA and showed no change in the striatum. Together, these findings strongly implicate SHC3 in the etiology of ND, which represents an important biological candidate for further investigation.

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Nicotine Metabolism and Intake in Black and White Smokers

Cited by 566 publications

References 26 publications

Differential success rates in racial groups: Results of a clinical trial of smoking cessation among female prisoners

Differential success rates in racial groups: Results of a clinical trial of smoking cessation among female prisoners

A novel CYP2A6 allele, CYP2A6*23, impairs enzyme function in vitro and in vivo and decreases smoking in a population of Black-African descent

Linkage and association studies in African- and Caucasian-American populations demonstrate that SHC3 is a novel susceptibility locus for nicotine dependence

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