A prospective study of the association between rate of nicotine metabolism and alcohol use in tobacco users in the United States

Roberts, Walter; Marotta, Phillip; Verplaetse, Terril L.; Peltier, MacKenzie R.; Burke, Catherine; Ramchandani, Vijay A.; McKee, Sherry A.

doi:10.1016/j.drugalcdep.2020.108210

Cited by 5 publications

(4 citation statements)

References 36 publications

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“…We also found that those reporting alcohol misuse were less likely to be fast metabolizers of nicotine. This was inconsistent with recent studies in the general population [ 27 , 28 ], which reported positive associations between alcohol consumption and NMR. Similarly, in a trial of men receiving treatment for alcohol use disorder, a 50% reduction in NMR was reported among those who successfully abstained from alcohol, compared to the baseline, despite little change in tobacco use, suggesting that chronic alcohol exposure induces CYP2A6 activity, which is responsible for nicotine metabolism [ 29 ].…”

Section: Discussioncontrasting

confidence: 99%

A Cross-Sectional Analysis of the Nicotine Metabolite Ratio and Its Association with Sociodemographic and Smoking Characteristics among People with HIV Who Smoke in South Africa

Keke

Wilson

Lebina

et al. 2023

IJERPH

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The nicotine metabolite ratio (NMR) is associated with race/ethnicity but has not been evaluated among smokers in the African region. We conducted a cross-sectional analysis of baseline data from a large randomized, controlled trial for smoking cessation among people with HIV (PWH) in South Africa. Urine samples were analyzed for the NMR and evaluated as a binary variable using a cutoff value of the fourth quartile to determine the fastest metabolizers. The median NMR was 0.31 (IQR: 0.31, 0.32; range: 0.29, 0.57); the cut-point for fast metabolizers was ≥0.3174 ng/mL. A high NMR was not associated with the number of cigarettes per day (OR = 1.10, 95% CI: 0.71, 1.70, p = 0.66) but was associated with 40% lower odds of a quit attempt in the past year (OR = 0.69; 95% CI: 0.44, 1.07, p = 0.09) and alcohol use (OR = 0.59, 95% CI: 0.32, 1.06, p = 0.07). No association was seen with marijuana or HIV clinical characteristics. As we found only minimal variability in the NMR and minimal associations with intensity of smoking, NMR may be of limited clinical value in this population, although it may inform which individuals are less likely to make a quit attempt.

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Section: Discussioncontrasting

confidence: 99%

A Cross-Sectional Analysis of the Nicotine Metabolite Ratio and Its Association with Sociodemographic and Smoking Characteristics among People with HIV Who Smoke in South Africa

Keke

Wilson

Lebina

et al. 2023

IJERPH

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“…For example, individuals who smoke and have a comorbid alcohol use disorder (AUD) are about half as likely to quit smoking as those without an AUD [ 119 ]. Higher NMR values have been prospectively linked to measures of alcohol consumption, including hazardous use [ 120 ]. The implications for using the NMR to guide the treatment of tobacco use among individuals with an AUD have yet to be explicated.…”

Section: Challenges and Opportunities For The Translation Of Biomarke...mentioning

confidence: 99%

The use of biomarkers to guide precision treatment for tobacco use

Siegel¹,

Tindle²,

Bergen³

et al. 2023

Addiction Neuroscience

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“…A biomarker for measuring CYP2A6 enzymatic activity is the nicotine metabolite ratio (NMR), the ratio of two nicotine metabolites, trans -3’-hydroxycotinine (3HC) to cotinine (COT) [ 2 ]. The NMR has been shown to be associated with smoking behaviors [ 1 ], smoking dose and risk of lung cancer [ 3 ], alcohol consumption [ 4 ], and smoking cessation [ 5 ]. As a result, there have been repeated calls for screening based on the NMR [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Predicting nicotine metabolism across ancestries using genotypes

et al. 2022

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Background There is a need to match characteristics of tobacco users with cessation treatments and risks of tobacco attributable diseases such as lung cancer. The rate in which the body metabolizes nicotine has proven an important predictor of these outcomes. Nicotine metabolism is primarily catalyzed by the enzyme cytochrone P450 (CYP2A6) and CYP2A6 activity can be measured as the ratio of two nicotine metabolites: trans-3’-hydroxycotinine to cotinine (NMR). Measurements of these metabolites are only possible in current tobacco users and vary by biofluid source, timing of collection, and protocols; unfortunately, this has limited their use in clinical practice. The NMR depends highly on genetic variation near CYP2A6 on chromosome 19 as well as ancestry, environmental, and other genetic factors. Thus, we aimed to develop prediction models of nicotine metabolism using genotypes and basic individual characteristics (age, gender, height, and weight). Results We identified four multiethnic studies with nicotine metabolites and DNA samples. We constructed a 263 marker panel from filtering genome-wide association scans of the NMR in each study. We then applied seven machine learning techniques to train models of nicotine metabolism on the largest and most ancestrally diverse dataset (N=2239). The models were then validated using the other three studies (total N=1415). Using cross-validation, we found the correlations between the observed and predicted NMR ranged from 0.69 to 0.97 depending on the model. When predictions were averaged in an ensemble model, the correlation was 0.81. The ensemble model generalizes well in the validation studies across ancestries, despite differences in the measurements of NMR between studies, with correlations of: 0.52 for African ancestry, 0.61 for Asian ancestry, and 0.46 for European ancestry. The most influential predictors of NMR identified in more than two models were rs56113850, rs11878604, and 21 other genetic variants near CYP2A6 as well as age and ancestry. Conclusions We have developed an ensemble of seven models for predicting the NMR across ancestries from genotypes and age, gender and BMI. These models were validated using three datasets and associate with nicotine dosages. The knowledge of how an individual metabolizes nicotine could be used to help select the optimal path to reducing or quitting tobacco use, as well as, evaluating risks of tobacco use.

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A prospective study of the association between rate of nicotine metabolism and alcohol use in tobacco users in the United States

Cited by 5 publications

References 36 publications

A Cross-Sectional Analysis of the Nicotine Metabolite Ratio and Its Association with Sociodemographic and Smoking Characteristics among People with HIV Who Smoke in South Africa

A Cross-Sectional Analysis of the Nicotine Metabolite Ratio and Its Association with Sociodemographic and Smoking Characteristics among People with HIV Who Smoke in South Africa

The use of biomarkers to guide precision treatment for tobacco use

Predicting nicotine metabolism across ancestries using genotypes

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