Association of ADH4 genetic variants with alcohol dependence risk and related phenotypes: results from a larger multicenter association study.
Genetic variants of the alcohol-metabolizing enzyme ADH4, located on chromosome 4q22-4q23, have been related to alcohol dependence (AD) risk in previous research. The aim of this association study in a large multicenter sample of alcohol-dependent individuals and controls is to confirm ADH4 single nucleotide polymorphism (SNP) and haplotype association with AD and relevant related phenotypes. One thousand, six hundred and twenty-two (1622) inpatient subjects and 1469 control subjects with DSM-IV. AD from four addiction treatment centres were included. Characteristics of AD and related phenotypes including alcohol withdrawal, Cloninger's type I and II and first ages of drinking, regular drinking and AD onset were obtained using standardized structured interviews. After subjects were genotyped for 2 ADH4 polymorphisms, single SNP case-control and haplotype analyses were conducted. Both variants--rs1800759 and rs1042364--and the A-A and C-G haplotypes were significantly related to AD across samples. Furthermore, associations with AD-related phenotypes and subtypes revealed a potential protective influence of this haplotype. This study confirms the significant relationship of ADH4 variants with AD and related phenotypes. While the rs1800759 and rs1042364 A-A haplotype had a potential protective influence on the risk for several AD-related phenotypes, this effect is rather small compared to functional variants of other alcohol or acetaldehyde-metabolizing enzymes like ALDH2*2 or ADH1B*2.
Preuss
Ulrich W
UW
Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University, Halle-Wittenberg, Julius-Kühn-Str. 7, D–06112 Halle, Germany. ulrich.preuss@medizin.uni-halle.de
Ridinger
Monika
M
Rujescu
Dan
D
Samochowiec
Jerzy
J
Fehr
Christoph
C
Wurst
Friedrich M
FM
Koller
Gabriele
G
Bondy
Brigitta
B
Wodarz
Norbert
N
Debniak
Tadeusz
T
Grzywacz
Anna
A
Soyka
Michael
M
Zill
Peter
P
D000328:Adult; D017668:Age of Onset; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000430:Alcohol Withdrawal Delirium / Q000235:genetics; D020270:Alcohol Withdrawal Seizures / Q000235:genetics; D000437:Alcoholism / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D005858:Germany; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011044:Poland; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial