Evidence map›Paper›PMID 22577853›Full record

ArticleAlcoholism, clinical and experimental research2012

Association between in vivo alcohol metabolism and genetic variation in pathways that metabolize the carbon skeleton of ethanol and NADH reoxidation in the alcohol challenge twin study.

Penelope A Lind, Stuart Macgregor, Andrew C Heath, Pamela A F Madden, Grant W Montgomery, Nicholas G Martin, John B Whitfield

Open access · greenAbstract readTwin Study
In one paragraph

Article in Alcoholism, clinical and experimental research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

8 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Genetics and genomics of alcohol sensitivity.Molecular genetics and genomics : MGG · 2014
    Review
  8. Review
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

7 authors at 2 institutions in 2 countries.

Penelope A LindMolecular Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia. Penelope.Lind@qimr.edu.au
Stuart Macgregor
Andrew C Heath
Pamela A F Madden
Grant W Montgomery
Nicholas G Martin
John B Whitfield
QIMR Berghofer Medical Research Institute · AUWashington University in St. Louis · US

Funding

PILOT--GENETIC EPIDEMIOLOGY OF ALCOHOL AND TOBACCO CONSUMPTION IN CHINESE SAMPLEP50AA011998 · NIAAA · WASHINGTON UNIVERSITY · PI TODD, RICHARD D · 1999 to 2008
$12.6M
THE GENETICS OF VULNERABILITY TO NICOTINE ADDICTIONSR01DA012854 · NIDA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN · 2000 to 2013
$10.4M
Resource CoreP60AA011998 · NIAAA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN · 2009 to 2013
$8.8M
Molecular Epidemiology of Alcoholism 3 - EDAC FamiliesR01AA013321 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 2001 to 2005
$4.3M
Molecular Epidemiology of Alcoholism 2- Big SibshipsR01AA013320 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 2003 to 2007
$3.1M
Genetic Epideniologic Models of Alcohol AbuseR37AA007728 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 1998 to 2007
$2.2M
VARIATION IN THE EFFECTS OF ALCOHOL ON LIVER FUNCTIONR01AA014041 · NIAAA · QUEENSLAND INSTITUTE OF MEDICAL RESEARCH · PI WHITFIELD, JOHN B · 2003 to 2007
$2.1M
GENE-ENVIRONMENT INTERPLAY IN ALCOHOLISMK05AA017688 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 2008 to 2017
$1.9M
Refining Phenotypic Measures of Nicotine WithdrawalK08DA019951 · NIDA · WASHINGTON UNIVERSITY · PI PERGADIA, MICHELE L · 2005 to 2009
$659k
The Genetics of Vulnerability to Nicotine AddictionsR56DA012854 · NIDA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN · 2007 to 2007
$436k
NATURAL HISTORY OF ALCOHOL USE &ABUSE--GENETIC MODELSR01AA007728 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 1988 to 1998
–
PERSISTENCE &CHANGE IN DRINKING HABITS: TWIN STUDYR01AA007535 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 1989 to 1996
–
NIAAA NIH HHS AA07728NIAAA NIH HHS AA11998NIAAA NIH HHS AA13320NIAAA NIH HHS AA13321NIAAA NIH HHS AA14041NIAAA NIH HHS AA17688NIAAA NIH HHS K05 AA017688NIAAA NIH HHS P50 AA011998NIAAA NIH HHS P60 AA011998NIAAA NIH HHS R01 AA007535NIAAA NIH HHS R01 AA007728NIAAA NIH HHS R01 AA013320NIAAA NIH HHS R01 AA013321NIAAA NIH HHS R01 AA014041NIAAA NIH HHS R37 AA007728NIDA NIH HHS DA012854NIDA NIH HHS DA019951NIDA NIH HHS K08 DA019951NIDA NIH HHS R01 DA012854NIDA NIH HHS R56 DA012854
6 · The paper itself

Abstract

backgroundVariation in alcohol metabolism affects the duration of intoxication and alcohol use. While the majority of genetic association studies investigating variation in alcohol metabolism have focused on polymorphisms in alcohol or aldehyde dehydrogenases, we have now tested for association with genes in alternative metabolic pathways that catalyze the carbon skeleton of ethanol (EtOH) and NADH reoxidation.

methodsNine hundred fifty single nucleotide polymorphisms (SNPs) spanning 14 genes (ACN9, ACSS1, ACSS2, ALDH1A1, CAT, CYP2E1, GOT1, GOT2, MDH1, MDH2, SLC25A10, SLC25A11, SLC25A12, SLC25A13) were genotyped in 352 young adults who participated in an alcohol challenge study. Traits tested were blood alcohol concentration (BAC), breath alcohol concentration (BrAC), peak alcohol concentration, and rates of alcohol absorption and elimination. Allelic association was tested using quantitative univariate and multivariate methods.

resultsA CYP2E1 promoter SNP (rs4838767, minor allele frequency 0.008) exceeded the threshold for study-wide significance (4.01 × 10(-5) ) for 2 early BAC, 8 BrAC measures, and the peak BrAC. For each phenotype, the minor C allele was related to a lower alcohol concentration, most strongly for the fourth BrAC (p = 2.07 × 10(-7) ) explaining ~8% of the phenotypic variance. We also observed suggestive patterns of association with variants in ALDH1A1 and on chromosome 17 near SLC25A11 for aspects of blood and breath alcohol metabolism. An SNP upstream of GOT1 (rs2490286) reached study-wide significance for multivariate BAC metabolism (p = 0.000040).

conclusionsOverall, we did not find strong evidence that variation in genes coding for proteins that further metabolize the carbon backbone of acetaldehyde, or contribute to mechanisms for regenerating NAD from NADH, affects alcohol metabolism in our European-descent subjects. However, based on the breath alcohol data, variation in the promoter of CYP2E1 may play a role in preabsorptive or early hepatic alcohol metabolism, but more samples are required to validate this finding.

Indexed as

AdolescentAdultCytochrome P-450 CYP2E1EthanolFemaleGene FrequencyGenetic VariationGenotypeHumansMaleNADOxidation-ReductionPhenotypePolymorphism, Single NucleotideTwins, DizygoticTwins, MonozygoticCytochrome P-450 CYP2E1EthanolNAD

Identifiers

PMID22577853
PMCPMC3729587
OpenAlexW2127696754

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.