title: Alcohol-metabolizing genes and alcohol phenotypes in an Israeli household sample.
abstract: BACKGROUND
  Alcohol dehydrogenase 1B and 1C (ADH1B and ADH1C) variants have been robustly associated with alcohol phenotypes in East Asian populations, but less so in non-Asian populations where prevalence of the most protective ADH1B allele is low (generally <5%). Further, the joint effects of ADH1B and ADH1C on alcohol phenotypes have been unclear. Therefore, we tested the independent and joint effects of ADH1B and ADH1C on alcohol phenotypes in an Israeli sample, with higher prevalence of the most protective ADH1B allele than other non-Asian populations.
  
  
  METHODS
  A structured interview assessed lifetime drinking and alcohol use disorders (AUDs) in adult Israeli household residents. Four single nucleotide polymorphisms (SNPs) were genotyped: ADH1B (rs1229984, rs1229982, and rs1159918) and ADH1C (rs698). Regression analysis examined the association between alcohol phenotypes and each SNP (absence vs. presence of the protective allele) as well as rs698/rs1229984 diplotypes (also indicating absence or presence of protective alleles) in lifetime drinkers (n = 1,129).
  
  
  RESULTS
  Lack of the ADH1B rs1229984 protective allele was significantly associated with consumption- and AUD-related phenotypes (OR = 1.77 for AUD; OR = 1.83 for risk drinking), while lack of the ADH1C rs698 protective allele was significantly associated with AUD-related phenotypes (OR = 2.32 for AUD). Diplotype analysis indicated that jointly ADH1B and ADH1C significantly influenced AUD-related phenotypes. For example, among those without protective alleles for ADH1B or ADH1C, OR for AUD was 1.87 as compared to those without the protective allele for ADH1B only and was 3.16 as compared to those with protective alleles for both ADH1B and ADH1C.
  
  
  CONCLUSIONS
  This study adds support for the relationship of ADH1B and ADH1C and alcohol phenotypes in non-Asians. Further, these findings help clarify the mixed results from previous studies by showing that ADH1B and ADH1C jointly effect AUDs, but not consumption. Studies of the association between alcohol phenotypes and either ADH1B or ADH1C alone may employ an oversimplified model, masking relevant information.
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Jacquelyn L
authors.initials: JL
authors.lastname: Meyers
authors.forename: Dvora
authors.initials: D
authors.lastname: Shmulewitz
authors.forename: Efrat
authors.initials: E
authors.lastname: Aharonovich
authors.forename: Rachel
authors.initials: R
authors.lastname: Waxman
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.forename: Baruch
authors.initials: B
authors.lastname: Spivak
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Hasin
mesh_terms: D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics*; D019973:Alcohol-Related Disorders / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D055815:Young Adult
chemical_list: C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase
keywords: Alcohol Consumption; Alcohol Dehydrogenase 1B; Alcohol Dehydrogenase 1C; Alcohol Use Disorders; Israel
references.citation: Alcohol Clin Exp Res. 2004 Jan;28(1):10-4
references.pmid: 14745297
references.citation: Drug Alcohol Depend. 2003 Jul 20;71(1):7-16
references.pmid: 12821201
references.citation: Drug Alcohol Depend. 1995 Jul;39(1):37-44
references.pmid: 7587973
references.citation: Alcohol Clin Exp Res. 2002 Sep;26(9):1315-21
references.pmid: 12351924
references.citation: Arch Gen Psychiatry. 2007 Nov;64(11):1313-20
references.pmid: 17984400
references.citation: Am J Hum Genet. 1991 Apr;48(4):677-81
references.pmid: 2014795
references.citation: J Subst Abuse. 1997;9:127-35
references.pmid: 9494944
references.citation: Addiction. 2006 Sep;101 Suppl 1:59-75
references.pmid: 16930162
references.citation: Alcohol Res Health. 2007;30(1):5-13
references.pmid: 17718394
references.citation: Genome Biol. 2012 Jan 25;13(1):R2
references.pmid: 22277159
references.citation: Dis Markers. 2011;31(5):267-77
references.pmid: 22048268
references.citation: Alcohol Clin Exp Res. 2009 May;33(5):761-71
references.pmid: 19298332
references.citation: Chem Biol Interact. 2011 May 30;191(1-3):38-41
references.pmid: 21168396
references.citation: Hum Genet. 2012 Aug;131(8):1361-74
references.pmid: 22476623
references.citation: Pharmacogenomics J. 2008 Jun;8(3):220-7
references.pmid: 17923853
references.citation: Am J Hum Genet. 2006 Jun;78(6):973-87
references.pmid: 16685648
references.citation: Nat Genet. 2012 Oct;44(10):1090-7
references.pmid: 22960999
references.citation: Hepatology. 1986 May-Jun;6(3):502-10
references.pmid: 3519419
references.citation: Hepatology. 2006 Feb;43(2):352-61
references.pmid: 16440362
references.citation: Lancet. 2009 Jun 27;373(9682):2223-33
references.pmid: 19560604
references.citation: Addict Biol. 2013 May;18(3):523-36
references.pmid: 22970887
references.citation: Am J Psychiatry. 2002 Aug;159(8):1432-4
references.pmid: 12153842
references.citation: J Stud Alcohol. 1998 Mar;59(2):133-9
references.pmid: 9500299
references.citation: Mol Psychiatry. 2012 Apr;17(4):445-50
references.pmid: 21968928
references.citation: Genetics. 1964 Oct;50:757-82
references.pmid: 14221879
references.citation: J Stud Alcohol Drugs. 2012 Nov;73(6):981-90
references.pmid: 23036217
references.citation: BMC Genet. 2010 Jun 14;11:48
references.pmid: 20546593
references.citation: Pharmacol Biochem Behav. 1983;18 Suppl 1:223-7
references.pmid: 6356161
references.citation: Biol Psychiatry. 2011 Sep 15;70(6):504-12
references.pmid: 21497796
references.citation: Genetics. 2000 Jun;155(2):945-59
references.pmid: 10835412
references.citation: Alcohol Clin Exp Res. 2012 Dec;36(12):2086-94
references.pmid: 22978509
references.citation: Am J Med Genet. 2000 Oct 9;96(5):632-7
references.pmid: 11054770
references.citation: J Biol Chem. 1990 Sep 25;265(27):16366-72
references.pmid: 2398055
references.citation: J Subst Abuse. 1998;10(4):341-53
references.pmid: 10897288
references.citation: Drug Alcohol Depend. 2010 Sep 1;111(1-2):146-54
references.pmid: 20537809
references.citation: Drug Alcohol Depend. 1997 Mar 14;44(2-3):133-41
references.pmid: 9088785
references.citation: Alcohol Clin Exp Res. 2007 Aug;31(8):1297-301
references.pmid: 17559546
references.citation: Am J Hum Genet. 2007 Oct;81(4):842-6
references.pmid: 17847010