[Molecular genetics of alcohol dependence].
Predisposition to alcohol dependence is affected by multiple environmental and genetic factors in complicated way. Family and twin studies estimated about 60% of hereditary rate for alcoholism. Many lines of evidence by divergent methods, e.g. gene-manipulated animals, linkage of human genome and genetic association studies, are accumulating for molecular genetic components involved in alcoholism. These studies have shown that genetic polymorphisms of the genes encoding alcohol metabolism enzymes and neurotransmitter signaling molecules in dopamine, GABA, opioid and serotonin systems, were substantially involved in individual variation of susceptibility to alcohol dependence. Recent whole-genome association examination using 500K gene-chip revealed that a set of genes of adhesion and cytoarchitecture molecules were also involved in the disorder. These unexpected new findings by gene-chip technology, which need to be confirmed by case-control association one by one, must bring about breakthrough in investigation of neural mechanisms of alcohol dependence and innovative therapy.
Ujike
Hiroshi
H
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D016022:Case-Control Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D011976:Receptors, Muscarinic / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics; D044348:Receptors, Serotonin, 5-HT2 / Q000235:genetics*
D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D017450:Receptors, Opioid, mu; D044348:Receptors, Serotonin, 5-HT2; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial