Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
About GenEpi
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
20958328
TITLE
The investigation into CYP2E1 in relation to the level of response to alcohol through a combination of linkage and association analysis.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
A low level of response to alcohol during an individual's early experience with alcohol is associated with an increase risk of alcoholism. A family-based genome-wide linkage analysis using sibling pairs that underwent an alcohol challenge where the level of response to alcohol was measured with the Subjective High Assessment Scale (SHAS) implicated the 10q terminal (10qter) region. CYP2E1, a gene known for its involvement with ethanol metabolism, maps to this region.
METHODS NlmCategory: METHODS
Variance component multipoint linkage analysis was performed on a combined map of single-nucleotide polymorphism (SNP) and microsatellite data. To account for the heterogeneity evident in the dataset, a calculation assuming locus heterogeneity was made using the Heterogeneity Log of Odds (HLOD) score. Association between SNP marker allele counts and copy number and SHAS scores were evaluated using a logistic regression model.
RESULTS NlmCategory: RESULTS
Linkage analysis detected significant linkage to CYP2E1, which was diminished because of apparent locus heterogeneity traced to a single family with extreme phenotypes. In retrospect, circumstances recorded during testing for this family suggest that their phenotype data are likely to be unreliable. Significant allelic associations were detected for several CYP2E1 polymorphisms and the SHAS score. DNA sequencing from families that contributed the greatest evidence for linkage did not detect any changes directly affecting the primary amino acid sequence. With the removal of a single family, combined evidence from microsatellites and SNPs offers significant linkage between the level of response to alcohol and the region on the end of chromosome 10.
CONCLUSION NlmCategory: CONCLUSIONS
Combined linkage and association indicate that sequence changes in or near CYP2E1 affect the level of response to alcohol providing a predictor of risk of alcoholism. The absence of coding sequence changes indicates that regulatory sequences are responsible. Implicating CYP2E1 in the level of response to alcohol allows inferences to be made about how the brain perceives alcohol.
Copyright © 2010 by the Research Society on Alcoholism.
DATE PUBLISHED
2011 Jan
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2010/10/19
entrez 2010/10/21 06:00
pubmed 2010/10/21 06:00
medline 2011/06/24 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Webb A Webb Amy A Department of Biomedical Engineering, University of North Carolina at Chapel Hill, USA.
Lind PA Lind Penelope A PA
Kalmijn J Kalmijn Jelger J
Feiler HS Feiler Heidi S HS
Smith TL Smith Tom L TL
Schuckit MA Schuckit Marc A MA
Wilhelmsen K Wilhelmsen Kirk K
INVESTIGATORS
JOURNAL
VOLUME: 35
ISSUE: 1
TITLE: Alcoholism, clinical and experimental research
ISOABBREVIATION: Alcohol. Clin. Exp. Res.
YEAR: 2011
MONTH: Jan
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1530-0277
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Alcohol Clin Exp Res
COUNTRY: England
ISSNLINKING: 0145-6008
NLMUNIQUEID: 7707242
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Psychol Med. 1999 Sep;29(5):1069-81 10576299
Cites Alcohol Res Health. 2006;29(4):245-54 17718403
Cites J Stud Alcohol. 1999 Nov;60(6):784-9 10606490
Cites Cancer Epidemiol Biomarkers Prev. 2000 Jun;9(6):551-6 10868687
Cites Alcohol Alcohol. 2000 May-Jun;35(3):242-8 10869242
Cites J Clin Pharm Ther. 2000 Jun;25(3):165-75 10886461
Cites Mol Pathol. 2000 Apr;53(2):88-93 10889908
Cites Int J Cancer. 2000 Sep 1;87(5):734-40 10925369
Cites Alcohol Clin Exp Res. 2001 Feb;25(2):221-7 11236836
Cites Oral Oncol. 2001 Jul;37(5):437-45 11377232
Cites Alcohol Clin Exp Res. 2001 Jun;25(6):800-4 11410713
Cites Alcohol Clin Exp Res. 2001 Jun;25(6 Suppl):11S-5S 11410734
Cites J Pharmacol Exp Ther. 2001 Nov;299(2):542-50 11602665
Cites Free Radic Biol Med. 2002 Jan 1;32(1):11-6 11755312
Cites Methods. 2001 Dec;25(4):402-8 11846609
Cites J Stud Alcohol. 2002 Jan;63(1):74-82 11925062
Cites Biochim Biophys Acta. 2003 Feb 17;1619(3):283-90 12573488
Cites Alcohol Clin Exp Res. 2003 May;27(5):812-7 12766626
Cites Alcohol Clin Exp Res. 2003 Jul;27(7):1041-7 12878909
Cites J Pharmacol Exp Ther. 2003 Sep;306(3):941-7 12750430
Cites Nucleic Acids Res. 1990 Dec 11;18(23):7194 1979861
Cites J Stud Alcohol. 1991 Sep;52(5):464-9 1943102
Cites Am J Psychiatry. 1992 Nov;149(11):1534-8 1415821
Cites Gastroenterology. 1995 Oct;109(4):1266-73 7557094
Cites J Biochem. 1994 Aug;116(2):321-6 7529759
Cites Cancer Res. 1992 Dec 1;52(23):6712-5 1423319
Cites Pharmacogenetics. 1995;5 Spec No:S141-4 7581484
Cites Arch Gen Psychiatry. 1996 Mar;53(3):202-10 8611056
Cites Arch Gen Psychiatry. 1996 Mar;53(3):258-63 8611063
Cites Alcohol Clin Exp Res. 1996 Feb;20(1):43-6 8651460
Cites Pharmacogenetics. 1995 Dec;5(6):351-7 8747406
Cites Pharmacogenetics. 1996 Apr;6(2):151-8 9156693
Cites Physiol Rev. 1997 Apr;77(2):517-44 9114822
Cites Carcinogenesis. 1997 May;18(5):967-73 9163682
Cites Int J Cancer. 1997 May 29;71(5):737-40 9180139
Cites Am J Psychiatry. 1997 Jul;154(7):983-8 9210750
Cites Am J Hum Genet. 1998 May;62(5):1198-211 9545414
Cites Pharmacogenetics. 1998 Aug;8(4):335-42 9731720
Cites Toxicol Appl Pharmacol. 1998 Sep;152(1):276-81 9772223
Cites Neuropsychobiology. 1998 Nov;38(4):218-21 9813460
Cites Biol Psychiatry. 1999 Mar 15;45(6):776-87 10188009
Cites Alcohol Clin Exp Res. 1999 Jun;23(6):991-1007 10397283
Cites J Hepatol. 2004 Nov;41(5):744-50 15519646
Cites Alcohol Clin Exp Res. 2005 Nov;29(11):1976-82 16340454
Cites Pharmacogenet Genomics. 2006 Jan;16(1):51-8 16344722
Cites Drug Metab Dispos. 2006 Apr;34(4):647-52 16434548
Cites Alcohol Clin Exp Res. 2006 Jul;30(7):1101-10 16792556
Cites Alcohol. 2006 Jun;39(2):73-9 17134659
Cites Nat Rev Cancer. 2007 Aug;7(8):599-612 17646865
Cites Genet Epidemiol. 1999;17 Suppl 1:S31-6 10597408
GRANTS
GRANTID AGENCY COUNTRY
AA05526 NIAAA NIH HHS United States
AA08403 NIAAA NIH HHS United States
M01 RR000083 NCRR NIH HHS United States
M01 RR000083-37S10426 NCRR NIH HHS United States
P20 RR020751 NCRR NIH HHS United States
P20 RR020751-03 NCRR NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Alcohol Drinking metabolism
Alcoholism genetics
Chromosomes, Human, Pair 10 genetics
Cytochrome P-450 CYP2E1 metabolism
DNA Copy Number Variations metabolism
Family metabolism
Female metabolism
Genetic Linkage metabolism
Genome-Wide Association Study metabolism
Genotype metabolism
Humans metabolism
Male metabolism
Parents metabolism
Polymorphism, Single Nucleotide metabolism
Risk Factors metabolism
Siblings metabolism
Smoking metabolism
Surveys and Questionnaires metabolism
Young Adult metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 1.14.13.- Cytochrome P-450 CYP2E1
OTHER ID's
OTHERID SOURCE
NIHMS230852 NLM
PMC3005010 NLM
Designed by: GenEpi IT
Maintained by: GenEpi IT
Feedback: webmaster
Copyright © 2007 QIMR
For more information Contact Us
epiit@qimr.edu.au
Last Modified: Oct 15 2007