Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify specific genes affecting vulnerability or resistance, we performed a whole-autosomal genome scan for genetic linkage to alcohol dependence in a Southwestern American Indian tribe. Genotypes at 517 autosomal microsatellite loci and clinical evaluations were available for 152 subjects belonging to extended pedigrees and forming 172 sib-pairs. Highly suggestive evidence for linkage emerged for two genomic regions using two- and multipoint sib-pair regression methods; both regions harbored neurogenetic candidate genes. The best evidence is seen with D11S1984 (nominal P = 0.00007, lod approximately equal to 3.1) on chromosome 11p, in close proximity to the DRD4 dopamine receptor and tyrosine hydroxylase (TH) genes. Good evidence is seen with D4S3242 (nominal P = 0.0002, lod approximately equal to 2.8) on chromosome 4p, near the beta1 GABA receptor gene. Interestingly, three loci in the alcohol dehydrogenase gene cluster on chromosome 4q showed evidence for linkage with two-point analyses, but not multipoint analysis.
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PMID:Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population. 960 7

Given the spectacular advances of genetics during the last five years, it seems appropriate to revisit the important subject of genetics of alcoholism and substance abuse. In recent studies alcohol abuse was shown to have an hereditability of roughly 38%, whereas psychostimulant and opiate use exhibit hereditabilities of 11 to 45%. The hereditability of smoking was found to be around 50%. There is a strong comorbidity between alcoholism and smoking. More than 80% of alcoholics smoke cigarettes in the U.S.A. Other genetic methods such as linkage analysis, allele sharing methods, association studies and analysis of inbred, transgenic and gene-knockout rodents, have partially agreed in showing that the 5HT-1B serotonin receptor and the DRD1, DRD2 and DRD4 dopamine receptors, as well as the dopamine transporter DAT, play an important role in behaviors related to alcoholism and substance abuse. Some neurochemical markers, as for example monoamine oxidase and adenylate cyclase have also been implicated in addictive disorders. The aldehyde dehydrogenase allele ALDH2*2 has a protective effect against alcoholism. Two whole genome linkage studies have shown linkage to chromosomal regions that are in the proximity of the DRD4 dopamine receptor, the GABA receptor gene cluster and the alcohol dehydrogenase gene cluster.
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PMID:[Genetics of addictive disorders]. 1134 17

Novel molecular genetic approaches, at genome-scale in different species allowed characterizing genes that have undergone recent selection. The interest in this research field is not limited to the natural curiosity about our evolutionary past, but it is also to identify novel susceptibility genes for neuropsychiatic disorders by pointing specific human traits, such as behavioral and cognitive abilities. Hypotheses have been proposed to relate specific psychiatric disorders to the origin of modern humans, as evidenced by the theory of Crow about schizophrenia. In the present review, we will focus on genes that underwent positive selection in humans or displayed a human specific evolutionary pattern and which were reported as associated with psychiatric disorders. This will include the (1) DRD4 gene associated with attentiondeficit/ hyperactivity disorder, located in a locus that underwent a positive selection; the (2) GABRB2 gene, a gene associated with schizophrenia and recently reported as the target of a positive selection; (3) MARK1, a candidate gene for autism that was reported as displaying a signature of adaptative evolution in the human lineage, and (4) the ADH and ALDH2 genes which are associated with alcoholism, and for which evidence of positive selection was identified in the human lineage since the divergence between humans and chimpanzees. Identification of novel candidate genes based on recent evolution selection, coupled to genome-wide strategies designed to detect rare structural variants, could lead to a better knowledge of the molecular mechanisms of neurodevelopmental disorders and might therefore help to develop new medical chemistry.
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PMID:Primate-accelerated evolutionary genes: novel routes to drug discovery in psychiatric disorders. 2016 40