Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Interaction between the Functional Polymorphisms of the Alcohol-Metabolism Genes in Protection against Alcoholism
Ist Teil von
American journal of human genetics, 1999-09, Vol.65 (3), p.795-807
Ort / Verlag
Chicago, IL: Elsevier Inc
Erscheinungsjahr
1999
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
The genes that encode the major enzymes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), exhibit functional polymorphism. The variant alleles
ADH2*2 and
ADH3*1, which encode high-activity ADH isoforms, and the
ALDH2*2 allele, which encodes the low-activity form of ALDH2, protect against alcoholism in East Asians. To investigate possible interactions among these protective genes, we genotyped 340 alcoholic and 545 control Han Chinese living in Taiwan at the
ADH2,
ADH3, and
ALDH2 loci. After the influence of
ALDH2*2 was controlled for, multiple logistic regression analysis indicated that allelic variation at
ADH3 exerts no significant effect on the risk of alcoholism. This can be accounted for by linkage disequlibrium between
ADH3*1 and
ADH2*2 ALDH2*2 homozygosity, regardless of the
ADH2 genotypes, was fully protective against alcoholism; no individual showing such homozygosity was found among the alcoholics. Logistic regression analyses of the remaining six combinatorial genotypes of the polymorphic
ADH2 and
ALDH2 loci indicated that individuals carrying one or two copies of
ADH2*2 and a single copy of
ALDH2*2 had the lowest risk (ORs 0.04–0.05) for alcoholism, as compared with the
ADH2*1/*1 and
ALDH2*1/*1 genotype. The disease risk associated with the
ADH2*2/*2-ALDH2*1/*1 genotype appeared to be about half of that associated with the
ADH2*1/*2-ALDH2*1/*1 genotype. The results suggest that protection afforded by the
ADH2*2 allele may be independent of that afforded by
ALDH2*2.