The association between alcoholism and the Taq1 "A" and "B" polymorphic alleles at the DRD2 gene and 48-bp tandem repeat in exon 3 of dopamine D4 receptor (DRD4) gene in 42 unrelated Slavic-surnamed patients and 76 normal controls was examined. The frequency of the A1 allele was higher in alcoholic patients and in alcoholic patients with a family history of alcoholism than in controls (χ²= 3.45, p < 0.001 and χ²)= 3.97, p < 0.001, respectively). Moreover, the frequency of the A1 allele was higher in alcoholics with a family history of alcoholism than in alcoholics without a family history (χ²= 3.33, p < 0.001).The results of association analysis for both the Taq1 "B" and DRD4 alleles were negative for alcoholics in general, subgroups of alcoholics and normal controls. However, the 7-repeat allele (DRD4*7R) of DRD4 gene occurred at significantly higher frequency in alcoholics with a family history of alcoholism compared with those without a family history (χ²= 3.42, p < 0.01).The results indicate that the A1 allele of the DRD2 gene is associated with susceptibility to alcoholism in general.The A1 allele, as well as the DRD4*7R allele, is significantly prevalent among alcoholics with a family history, in comparison with alcoholics without a family history, reflecting different roles of genetic factors in development of alcoholism.
We provide an overview of the recent achievements in psychiatric genetics research in the Russian Federation and present genotype-phenotype, population, epigenetic, cytogenetic, functional, ENIGMA, and pharmacogenetic studies, with an emphasis on genome-wide association studies. The genetic backgrounds of mental illnesses in the polyethnic and multicultural population of the Russian Federation are still understudied. Furthermore, genetic, genomic, and pharmacogenetic data from the Russian Federation are not adequately represented in the international scientific literature, are currently not available for meta-analyses and have never been compared with data from other populations. Most of these problems cannot be solved by individual centers working in isolation but warrant a truly collaborative effort that brings together all the major psychiatric genetic research centers in the Russian Federation in a national consortium. For this reason, we have established the Russian National Consortium for Psychiatric Genetics (RNCPG) with the aim to strengthen the power and rigor of psychiatric genetics research in the Russian Federation and enhance the international compatibility of this research.The consortium is set up as an open organization that will facilitate collaborations on complex biomedical research projects in human mental health in the Russian Federation and abroad. These projects will include genotyping, sequencing, transcriptome and epigenome analysis, metabolomics, and a wide array of other state-of-the-art analyses. Here, we discuss the challenges we face and the approaches we will take to unlock the huge potential that the Russian Federation holds for the worldwide psychiatric genetics community.
Dopamine content of blood, activity of adenylate- and guanylate cyclases in platelets and lymphocytes, catechol-O-methyltransferase in erythrocytes, dopamine-beta-hydroxylase in blood plasma, monoamine oxidase in platelets, cAMP and cGMP content of blood, and the intensity of 3H-DA uptake by platelets have been investigated in alcoholic patients at different clinical states. Most of these indices have been studied in the brain and blood of rats displaying different affinities to alcohol. The results indicate that, in addition to the previously described disturbances of DA turnover, changes occur in the functions of enzyme and receptor systems involved in the mechanism of catecholamine neuromediation. Rats preferring and avoiding alcohol exhibit different DA and cyclic nucleotide concentrations in the blood and a trend towards different activity of some enzymes in the brain. It is suggested that: (1) the disturbances in the regulation of catecholamine neuromediation are involved in the mechanism of development of alcohol dependence; (2) the genetically-determined abnormalities of catecholamine neuromediation may contribute to an individual's attitude to alcohol.
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