Evidence map›Paper›PMID 24448396›Full record

ArticlePharmacogenetics and genomics2014

Variation in P450 oxidoreductase (POR) A503V and flavin-containing monooxygenase (FMO)-3 E158K is associated with minor alterations in nicotine metabolism, but does not alter cigarette consumption.

Meghan J Chenoweth, Andy Z X Zhu, Lisa Sanderson Cox, Jasjit S Ahluwalia, Neal L Benowitz, Rachel F Tyndale

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmacogenetics and genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Rapid detection ofMolecular medicine reports · 2022
    Article
  5. Article
  6. Review
  7. Article
  8. Nicotine-Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019
    Article
  9. Article
  10. Article
  11. Variation in CYP2A6 Activity and Personalized Medicine.Journal of personalized medicine · 2017
    Review
  12. Article
  13. Article
  14. Article
  15. Protective Role of Crocin Against Nicotine-induced Damages on Male Mice Liver.International journal of preventive medicine · 2015
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 5 institutions in 2 countries.

Meghan J ChenowethaDepartments of Psychiatry and Pharmacology and Toxicology, Centre for Addiction and Mental Health (CAMH), Campbell Family Mental Health Research Institute, University of Toronto, Toronto, Ontario, Canada bDepartment of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kansas cDepartment of Medicine and Center for Health Equity, University of Minnesota Medical School, Minneapolis, Minnesota dDivision of Clinical Pharmacology and Experimental Therapeutics, Departments of Medicine and Bioengineering & Therapeutic Sciences, University of California, San Francisco, California, USA.
Andy Z X Zhu
Lisa Sanderson Cox
Jasjit S Ahluwalia
Neal L Benowitz
Rachel F Tyndale
University of Toronto · CACentre for Addiction and Mental Health · CAUniversity of California, San Francisco · USUniversity of Kansas · USUniversity of Minnesota Medical Center · US

Funding

University of Toronto Coordinating Genetics Core & Clinical Trial SiteU01DA020830 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI LERMAN, CARYN, TYNDALE, RACHEL FYNVOLA · 2005 to 2014
$22.4M
Helping African American Light Smokers QuitR01CA091912 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI COX, LISA SANDERSON · 2001 to 2010
$5.6M
CIHR MOP86471CIHR TMH-109787NCI NIH HHS CA091912NCI NIH HHS R01 CA091912NIDA NIH HHS DA020830NIDA NIH HHS U01 DA020830
6 · The paper itself

Abstract

The rates of nicotine metabolism differ widely, even after controlling for genetic variation in the major nicotine-metabolizing enzyme, CYP2A6. Genetic variants in an additional nicotine-metabolizing enzyme, flavin-containing monooxygenase (FMO)-3, and an obligate microsomal CYP-supportive enzyme, cytochrome P450 oxidoreductase (POR), were investigated. We examined the impact of FMO3 E158K and POR A503V before and after stratifying by CYP2A6 metabolism group. In 130 nonsmokers of African descent who received 4 mg oral nicotine, FMO3 158K trended toward slower nicotine metabolism in reduced CYP2A6 metabolizers (P=0.07) only, whereas POR 503V was associated with faster CYP2A6 activity (nicotine metabolite ratio) in normal (P=0.03), but not reduced, CYP2A6 metabolizers. Neither FMO3 158K nor POR 503V significantly altered the nicotine metabolic ratio (N=659), cigarette consumption (N=667), or urine total nicotine equivalents (N=418) in smokers of African descent. Thus, FMO3 E158K and POR A503V are minor sources of nicotine metabolism variation, insufficient to appreciably alter smoking.

Indexed as

Aryl Hydrocarbon HydroxylasesBlack PeopleCytochrome P-450 CYP2A6Genetic Association StudiesGenetic VariationGenotypeHumansMetabolic Clearance RateNADPH-Ferrihemoprotein ReductaseNicotineOxygenasesPolymorphism, Single NucleotideSmokingAryl Hydrocarbon HydroxylasesCYP2A6 protein, humanCytochrome P-450 CYP2A6dimethylaniline monooxygenase (N-oxide forming)NADPH-Ferrihemoprotein ReductaseNicotineOxygenases

Identifiers

PMID24448396
PMCPMC3985268
OpenAlexW1968319279

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.