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The nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine) is a stable biomarker for CYP2A6 enzyme activity and nicotine clearance, with demonstrated clinical utility in personalizing smoking cessation treatment. Common genetic variation in the CYP2A6 region is strongly associated with NMR in smokers. Here, we investigated this regional association in more detail. We evaluated the association of CYP2A6 single-nucleotide polymorphisms (SNPs) and * alleles with NMR among African American smokers (N = 953) from two clinical trials of smoking cessation. Stepwise conditional analysis and Bayesian fine-mapping were undertaken. Putative causal variants were incorporated into an existing African ancestry-specific genetic risk score (GRS) for NMR, and the performance of the updated GRS was evaluated in both African American (n = 953) and European ancestry smokers (n = 933) from these clinical trials. Five independent associations with NMR in the CYP2A6 region were identified using stepwise conditional analysis, including the deletion variant CYP2A6*4 (beta = -0.90, p = 1.55 × 10-11). Six putative causal variants were identified using Bayesian fine-mapping (posterior probability, PP = 0.67), with the top causal configuration including CYP2A6*4, rs116670633, CYP2A6*9, rs28399451, rs8192720, and rs10853742 (PP = 0.09). Incorporating these putative causal variants into an existing ancestry-specific GRS resulted in comparable prediction of NMR within African American smokers, and improved trans-ancestry portability of the GRS to European smokers. Our findings suggest that both * alleles and SNPs underlie the association of the CYP2A6 region with NMR among African American smokers, identify a shortlist of variants that may causally influence nicotine clearance, and suggest that portability of GRSs across populations can be improved through inclusion of putative causal variants.
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Varenicline, the most efficacious smoking cessation monotherapy, produces abnormal dreams. Although genetic contributions to varenicline-associated nausea and cessation have been identified, the role of genetics in abnormal dreams is unknown. We conducted a genomewide association study (GWAS) of abnormal dreams in 188 European ancestry smokers treated with varenicline (NCT01314001). Additive genetic models examined the likelihood of experiencing abnormal dreams 2 weeks following varenicline initiation. For the top locus, we tested for selectivity to varenicline, effects on cessation, replication, and generalizability to African ancestry (AA) individuals. The top GWAS variant associated with abnormal dreams was rs901886, mapping to intron 2 of ICAM5 on chromosome 19. The prevalence of abnormal dreams in those with rs901886 CC, CT, and TT genotypes was 15%, 36%, and 62%, respectively (odds ratio = 2.94 for T vs. C, 95% confidence interval = 1.92-4.55, P = 2.03e-7; T allele frequency = 52%). This rs901886 association was selective to varenicline (P values > 0.05 on nicotine patch and placebo). There were also positive associations for rs901886 T (vs. C allele, P = 0.03) and for abnormal dreams (P = 0.06) with varenicline-aided cessation. Neither rs901886 (P = 0.40) nor abnormal dreams (P = 0.24) were associated with adherence. A similar direction of effect of rs901886 on abnormal dreams was observed in a second varenicline trial (NCT01836276). In AA individuals (n = 137), rs901886 was not associated with abnormal dreams (P = 0.41), but there was an association for a variant located ~ 74.4 kb 5' of ICAM5 (P = 2.56e-3). Variation in ICAM5 may influence abnormal dreams and cessation on varenicline. These findings provide additional support for genetically optimized smoking cessation approaches.
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Sueños , Estudio de Asociación del Genoma Completo , Agentes para el Cese del Hábito de Fumar , Cese del Hábito de Fumar , Vareniclina , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sueños/efectos de los fármacos , Polimorfismo de Nucleótido Simple , Cese del Hábito de Fumar/métodos , Agentes para el Cese del Hábito de Fumar/efectos adversos , Agentes para el Cese del Hábito de Fumar/uso terapéutico , Vareniclina/efectos adversosRESUMEN
OBJECTIVE: Provide evidence on racial and ethnic differences in biomarkers of exposure from rising e-cigarette use among U.S. adults. METHODS: Data were drawn from Waves 1-5 of the Population Assessment of Tobacco and Health study (September 2013-November 2019). Differences in biomarkers of exposure and potential harm (BOE/BoPH) across non-Hispanic (NH)-Whites, NH Blacks, Hispanic/Latinos, and NH others were examined using generalized estimation equations. RESULTS: Among exclusive e-cigarette users, mean concentrations of BOEs/BoPHs were not significantly different across NH Blacks (n=97), NH others (n=122), and NH Whites (n=1062), after adjustment by wave, age, sex, education, exposure to the secondhand smoke, and the number of recent puffs. Compared to NH Whites, Hispanics (n=151) had lower concentrations of nicotine equivalents (0.5[0.2-1.7] vs. 15.5 [12.5-19.1] nmol/mg creatinine, p<.0001), cotinine (33.4[9.7-114.7] vs. 1008.3 [808.3-1257.9] ng/mg creatinine, p<.0001), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) (2.6[1.5-4.4] vs. 5.7 [4.9-6.6] pg/mg creatinine, p=.004), but similar concentrations of BOEs for heavy metals, polycyclic aromatic hydrocarbons, volatile organic compounds, and oxidative stress. Differences between Hispanics and NH Whites are expected, given different e-cigarette use profiles. Specifically, Hispanics were less likely to be daily vapers (49.4[35.1-63.8]% vs 81.3[77.7-84.5]%, p<.0001) and nicotine e-cigarette users (72.7 [64.0-79.9]% vs. 89.2 [86.4-91.5]%, p=.0002] and reported a lower number of recent puffs (mean[standard error]=16.7[3.6] vs. 28.6[2.0], p=.02] than their NH-White counterparts. Hispanic vapers were also less likely than NH Whites to have previously smoked cigarettes (49.7 [37.2-62.3]% vs. 88.5 [84.7-91.5]%, p<.0001]). CONCLUSIONS: Hispanic vapers exhibited lower exposure to nicotine metabolites and carcinogens than their non-Hispanic White counterparts. The harm reduction potential from e-cigarette use are likely to be realized across diverse racial and ethnic groups.
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Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Adulto , Humanos , Nicotina/efectos adversos , Nicotina/metabolismo , Creatinina , Biomarcadores/químicaRESUMEN
As opposed to smoking cessation with nicotine-replacement therapy and/or varenicline, nicotine-containing e-cigarette use does not improve some airway inflammatory markers. https://bit.ly/3FyqIt9.
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BACKGROUND AND AIMS: CYP2B6, a genetically variable enzyme, converts bupropion to its active metabolite hydroxybupropion. CYP2B6 activity and bupropion-aided cessation differ between women and men. The aim of this study was to determine whether genetically normal (versus reduced) CYP2B6 activity increases bupropion-aided cessation in African American smokers via higher hydroxybupropion concentration, and whether this differs by sex. DESIGN AND SETTING: Secondary analysis of a smoking cessation clinical trial (NCT00666978). PARTICIPANTS/CASES: African American light smokers (≤ 10 cigarettes/day). INTERVENTIONS: Participants were treated with bupropion for 7 weeks. MEASUREMENTS: Participants with detectable bupropion and/or hydroxybupropion concentrations were divided into normal (n = 64) and reduced (n = 109) CYP2B6 activity groups based on the presence of decreased-function CYP2B6*6 and CYP2B6*18 alleles. Biochemically verified smoking cessation was assessed at week 3, end of treatment (7 weeks) and follow-up (26 weeks). FINDINGS: Normal (versus reduced) CYP2B6 activity was associated with increased cessation at week 7, which was mediated by higher hydroxybupropion concentration [odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.03, 1.78]; this mediation effect persisted at week 26 (OR = 1.23, 95% CI = 1.02, 1.70). The mediation effect was similar in women (n = 116; OR = 1.33, 95% CI = 1.01, 2.30) and men (n = 57; OR = 1.33, 95% CI = 0.92, 3.87). Moreover, sex did not appear to moderate the mediation effect, although this should be tested in a larger sample. CONCLUSIONS: In African American light smokers with verified early bupropion use, genetically normal CYP2B6 activity appears to be indirectly associated with greater smoking cessation success in a relationship mediated by higher hydroxybupropion concentration. The mediating effect of higher hydroxybupropion concentration on smoking cessation persists beyond the active treatment phase and does not appear to differ by sex.
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Bupropión , Cese del Hábito de Fumar , Negro o Afroamericano , Bupropión/análogos & derivados , Bupropión/uso terapéutico , Citocromo P-450 CYP2B6/genética , Femenino , Humanos , Masculino , Análisis de MediaciónRESUMEN
Nicotine is inactivated by the polymorphic CYP2A6 enzyme to cotinine and then to 3'hydroxycotinine. The Nicotine Metabolite Ratio (NMR; 3'hydroxycotinine/cotinine) is a heritable nicotine metabolism biomarker, varies with sex and ancestry, and influences smoking cessation and disease risk. We conducted sex-stratified genome-wide association studies of the NMR in European American (EA) and African American (AA) smokers (NCT01314001, NCT00666978). In EA females (n = 389) and males (n = 541), one significant (P < 5e-8) chromosome 19 locus was found (top variant: rs56113850, CYP2A6 (intronic), for C vs. T: females: beta = 0.67, P = 7.5e-22, 21.8% variation explained; males: beta = 0.75, P = 1.2e-37, 26.1% variation explained). In AA females (n = 503) and males (n = 352), the top variant was found on chromosome 19 but differed by sex (females: rs11878604, CYP2A6 (~ 16 kb 3'), for C vs. T: beta = - 0.71, P = 6.6e-26, 16.2% variation explained; males: rs3865454, CYP2A6 (~ 7 kb 3'), for G vs. T: beta = 0.64, P = 1.9e-19, 18.9% variation explained). In AA females, a significant region was found on chromosome 12 (top variant: rs12425845: P = 5.0e-9, TMEM132C (~ 1 Mb 5'), 6.1% variation explained) which was not significant in AA males. In AA males, significant regions were found on chromosomes 6 (top variant: rs9379805: P = 4.8e-9, SLC17A2 (~ 8 kb 5'), 8.0% variation explained) and 16 (top variant: rs77368288: P = 3.5e-8, ZNF469 (~ 92 kb 5'), 7.1% variation explained) which were not significant in AA females. Further investigation of these associations outside of chromosome 19 is required, as they did not replicate. Understanding how sex and ancestry influence nicotine metabolism genetics may improve personalized approaches for smoking cessation and risk prediction for tobacco-related diseases.
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Negro o Afroamericano/genética , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Nicotina/metabolismo , Población Blanca/genética , Alelos , Mapeo Cromosómico , Femenino , Genotipo , Humanos , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Carácter Cuantitativo Heredable , Factores Sexuales , FumarRESUMEN
Psychometric critiques of cross-cultural research emphasize testing whether instruments measure the same construct across cultural groups. We tested for measurement invariance (by race/ethnicity) of instruments used to evaluate the relationship between alcohol and tobacco use with perceived discrimination and socioeconomic status (SES). Tests of psychometric equivalence across race/ethnicity focused on: the latent organization of constructs (configural invariance); if observed indicators have equal factor loadings or "true score" variance (metric invariance); and whether manifest indicators change uniformly contingent on change in the latent variable (scalar invariance). A cross-sectional survey of 2,376 cigarette smokers (794 Black, 786 Latinx, 796 White; mean age = 43 [SD = 12]; 58% female) was recruited via an online research panel. Discrimination was indicated by self-report; SES was indicated by self-reported education, employment, income, and the "SES Ladder;" alcohol use was indicated by frequency and typical quantity of drinking, and frequency of heavy drinking; tobacco use was indicated by frequency of smoking, cigarettes per smoking day, and time to first cigarette. All instruments demonstrated configural invariance; either full metric invariance (alcohol and discrimination) or partial metric invariance (tobacco and SES); and all constructs demonstrated partial scalar invariance. Results support psychometric critiques; for example, all of the SES indicators violated assumptions of classical measurement theory for valid between group comparisons. All of our instruments displayed some degree of systematic bias in measurement across race/ethnicity. Studies testing ethnic/racial differences may need to move beyond classical measurement theory, and may benefit from using statistical approaches that can test for (and model) bias in measurement. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Consumo de Bebidas Alcohólicas/etnología , Fumar Cigarrillos/etnología , Etnicidad/estadística & datos numéricos , Determinantes Sociales de la Salud , Adulto , Negro o Afroamericano/estadística & datos numéricos , Consumo de Bebidas Alcohólicas/epidemiología , Sesgo , Fumar Cigarrillos/epidemiología , Estudios Transversales , Escolaridad , Empleo/estadística & datos numéricos , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Renta/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Autoinforme , Productos de Tabaco , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND AND AIMS: The activity of CYP2A6, the major nicotine-inactivating enzyme, is measurable in smokers using the nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine). Due to its role in nicotine clearance, the NMR is associated with smoking behaviours and response to pharmacotherapies. The NMR is highly heritable (~80%), and on average lower in African Americans (AA) versus whites. We previously identified several reduce and loss-of-function CYP2A6 variants common in individuals of African descent. Our current aim was to identify novel genetic influences on the NMR in AA smokers using genome-wide approaches. DESIGN: Genome-wide association study (GWAS). SETTING: Multiple sites within Canada and the United States. PARTICIPANTS: AA smokers from two clinical trials: Pharmacogenetics of Nicotine Addiction Treatment (PNAT)-2 (NCT01314001; n = 504) and Kick-it-at-Swope (KIS)-3 (NCT00666978; n = 450). MEASUREMENTS: Genome-wide SNP genotyping, the NMR (phenotype) and population substructure and NMR covariates. FINDINGS: Meta-analysis revealed three independent chromosome 19 signals (rs12459249, rs111645190 and rs185430475) associated with the NMR. The top overall hit, rs12459249 (P = 1.47e-39; beta = 0.59 per C (versus T) allele, SE = 0.045), located ~9.5 kb 3' of CYP2A6, remained genome-wide significant after controlling for the common (~10% in AA) non-functional CYP2A6*17 allele. In contrast, rs111645190 and rs185430475 were not genome-wide significant when controlling for CYP2A6*17. In total, 96 signals associated with the NMR were identified; many were not found in prior NMR GWASs in individuals of European descent. The top hits were also associated with the NMR in a third cohort of AA (KIS2; n = 480). None of the hits were in UGT or OCT2 genes. CONCLUSIONS: Three independent chromosome 19 signals account for ~20% of the variability in the nicotine metabolite ratio in African American smokers. The hits identified may contribute to inter-ethnic variability in nicotine metabolism, smoking behaviours and tobacco-related disease risk.
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Cromosomas Humanos Par 19/metabolismo , Citocromo P-450 CYP2A6/sangre , Estudio de Asociación del Genoma Completo/estadística & datos numéricos , Nicotina/sangre , Fumar/sangre , Fumar/genética , Adulto , Negro o Afroamericano , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Canadá , Cromosomas Humanos Par 19/enzimología , Cromosomas Humanos Par 19/genética , Citocromo P-450 CYP2A6/genética , Femenino , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Nicotina/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Fumadores/estadística & datos numéricos , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Other forms of tobacco use are increasing in prevalence, yet most tobacco control efforts are aimed at cigarettes. In light of this, it is important to identify individuals who are using both cigarettes and alternative tobacco products (ATPs). Most previous studies have used regression models. We conducted a traditional logistic regression model and a classification and regression tree (CART) model to illustrate and discuss the added advantages of using CART in the setting of identifying high-risk subgroups of ATP users among cigarettes smokers. METHODS: The data were collected from an online cross-sectional survey administered by Survey Sampling International between July 5, 2012 and August 15, 2012. Eligible participants self-identified as current smokers, African American, White, or Latino (of any race), were English-speaking, and were at least 25 years old. The study sample included 2,376 participants and was divided into independent training and validation samples for a hold out validation. Logistic regression and CART models were used to examine the important predictors of cigarettes + ATP users. RESULTS: The logistic regression model identified nine important factors: gender, age, race, nicotine dependence, buying cigarettes or borrowing, whether the price of cigarettes influences the brand purchased, whether the participants set limits on cigarettes per day, alcohol use scores, and discrimination frequencies. The C-index of the logistic regression model was 0.74, indicating good discriminatory capability. The model performed well in the validation cohort also with good discrimination (c-index = 0.73) and excellent calibration (R-square = 0.96 in the calibration regression). The parsimonious CART model identified gender, age, alcohol use score, race, and discrimination frequencies to be the most important factors. It also revealed interesting partial interactions. The c-index is 0.70 for the training sample and 0.69 for the validation sample. The misclassification rate was 0.342 for the training sample and 0.346 for the validation sample. The CART model was easier to interpret and discovered target populations that possess clinical significance. CONCLUSION: This study suggests that the non-parametric CART model is parsimonious, potentially easier to interpret, and provides additional information in identifying the subgroups at high risk of ATP use among cigarette smokers.
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Grupos Raciales/estadística & datos numéricos , Fumar/epidemiología , Productos de Tabaco/estadística & datos numéricos , Tabaquismo/epidemiología , Adulto , Negro o Afroamericano , Factores de Edad , Consumo de Bebidas Alcohólicas/epidemiología , Comercio , Estudios Transversales , Femenino , Hispánicos o Latinos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Fumar/etnología , Tabaquismo/etnología , Población BlancaRESUMEN
BACKGROUND: Pediatric obesity is a serious and prevalent problem. Smartphone technology, which is becoming increasingly available to children of diverse backgrounds, presents a unique opportunity to instill healthy behaviors before the onset of obesity. Past studies have examined the use of smartphone applications as tools of health behavior modification for adults. The present study examines the content of children's exercise and nutrition smartphone apps. METHOD: Sixty-two iPhone apps were identified and coded by two independent raters for adherence to expert-recommended behaviors (e.g., five fruits/vegetables per day) and strategies (e.g., self-monitoring diet/physical activity) for the prevention of pediatric obesity. RESULTS: App behavioral and strategy index scores were uniformly low. Apps were more likely to address expert-recommended behaviors for the prevention of pediatric obesity (93.5%), whereas few apps addressed recommended strategies (20.9%). The most common behaviors addressed included physical activity (53.2%) and fruit/vegetable consumption (48.3%). Other important behaviors (e.g., screen time [1.6%] and family meals together [1.6%]) were rarely addressed. CONCLUSIONS: Current children's diet and exercise apps could be improved with increased adherence to expert-recommended guidelines, especially expert-recommended strategies.
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Teléfono Celular , Computadoras de Mano , Adhesión a Directriz , Conductas Relacionadas con la Salud , Promoción de la Salud , Obesidad Infantil/prevención & control , Adolescente , Actitud hacia los Computadores , Niño , Dieta , Medicina Basada en la Evidencia , Ejercicio Físico , Conducta Alimentaria , Femenino , Promoción de la Salud/métodos , Humanos , Masculino , Guías de Práctica Clínica como Asunto , Programas InformáticosRESUMEN
Given the increased prevalence of non-daily smoking and changes in smoking patterns, particularly among young adults, we examined correlates of smoking level, specifically motives for smoking, and readiness to quit smoking among 2682 college undergraduates who completed an online survey. Overall, 64.7% (n = 1736) were non-smokers, 11.6% (n = 312) smoked 1-5 days, 10.5% (n = 281) smoked 6-29 days and 13.2% (n = 353) were daily smokers. Ordinal regression analyses modeling smoking level indicated that correlates of higher smoking level included having more friends who smoke (ß = 0.63, 95% CI 0.57-0.69) and more frequent other tobacco use (ß = 0.04, 95% CI 0.02-0.05), drinking (ß = 0.04, 95% CI 0.02-0.07) and binge drinking (ß = 0.09, 95% CI 0.06-0.13). Bivariate analyses indicated that daily smokers (versus the subgroups of non-daily smokers) were less likely to smoke for social reasons but more likely to smoke for self-confidence, boredom, and affect regulation. Controlling for sociodemographics, correlates of readiness to quit among current smokers included fewer friends who smoke (P = 0.002), less frequent binge drinking (P = 0.03), being a social smoker (P < 0.001), smoking less for self-confidence (P = 0.04), smoking more for boredom (P = 0.03) and less frequent smoking (P = 0.001). Specific motives for smoking and potential barriers to cessation particularly may be relevant to different groups of college student smokers.
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Cese del Hábito de Fumar/psicología , Fumar/epidemiología , Estudiantes/psicología , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Alcoholismo/epidemiología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Minnesota/epidemiología , Fumar/psicología , Factores Socioeconómicos , Estudiantes/estadística & datos numéricos , Universidades , Adulto JovenRESUMEN
OBJECTIVE: To assess rates of overweight/obesity and related health behaviors among rural and urban children using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: Data were drawn from the 2003-2004 and 2005-2006 NHANES surveys regarding demographic characteristics, weight status, dietary behaviors and physical activity behaviors. RESULTS: Significantly more rural children were found to be obese than urban children. Health behavior differences to explain this differential obesity rate were primarily not significant, but multivariate analyses indicate that for rural children meeting physical activity recommendations is protective and engaging in more than 2 hr/day of electronic entertainment promotes obesity. CONCLUSIONS: There are modifiable health behavior differences between rural and urban children which may account for the significantly higher obesity rates among rural children.