Characterization of polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 and relationship to the alcoholism in a Colombian population
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Identify and characterize polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 in a Colombian population residing in the city of Bogotá and determine its possible relationship to the alcoholism.
ADH2, ADH3, ALDH2, and CYP2E1 genotypes a population of 148 individuals with non-problematic alcohol and 65 individuals with alcoholism were determined with TaqMan probes and PCR-RFLP. DNA was obtained from peripheral blood white cells.
Significant difference was found in family history of alcoholism and use of other psychoactive substances to compare alcoholics with controls. When allelic frequencies for each category (gender) were considered, frequency of A2 allele carriers in ADH2 was found higher in male patients than controls. In women, the relative frequency for c1 allele in CYP2E1 was lower in controls than alcoholics. The ALDH2 locus is monomorphic. No significant differences in allele distributions of the loci examined to compare two populations were observed, however when stratifying the same trend was found that these differences tended to be significant.
This study allows us to conclude the positive association between family history of alcoholism and alcoholism suggesting that there is a favourable hereditary predisposition. Since substance dependence requires interaction of multiple genes, the combination of genotypes ADH2 * 2, CYP2E1 * 1 combined with genotype homozygous ALDH2 * 1 found in this study could be leading to the population to a potential risk to alcoholism.
WHO . Global status report on alcohol and health. Library Cataloguing-in-Publication Data; Italia: 2011. http://www.who.int/substance_abuse/publications/global_alcohol_report/msbgsruprofiles.pdf.
Higuchi S, Matsushita S, Masaki T, Yokoyama A, Kimura M, Suzuki G, et al. Influence of genetic variations of ethanol-metabolizing enzymes on phenotypes of alcohol-related disorders. Ann N Y Acad Sci. 2004;1025(1):472–480.
Konishi T, Luo H, Calvillo M , Mayo MS , Lin KM , Wan YJ . ADH1B*1, ADH1C*2, DRD2 (141C Ins), and 5-HTTLPR are associated with alcoholism in Mexican American men living in los Angeles. Alcohol Clin Exp Res. 2004;28:1145–1152.
Edenberg H. The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res Health. 2007;30:5–13.
Duranceaux N, Schuckit M, Eng MY, Robinson SK, Carr LG, Wall TL. Associations of Variations in Alcohol Dehydrogenase Genes with the Level of Response to Alcohol in Non-Asians. Alcohol Clin Exp Res. 2006;30:1470–1478.
Takagi S, Iwai N, Yamauchi R, Kojima S, Yasuno S, Baba T, et al. Aldehyde dehydrogenase 2 gene is a risk factor for myocardial infarction in Japanese men. Hypertens Res. 2002;25:677–681.
Larson H, Weiner H, Hurley TD. Disruption of the coenzyme binding site and dimer interface revealed in the crystal structure of mitochondrial aldehyde dehydrogenase "Asian" variant. J Biol Chem. 2005;280:30550–30556.
Choi IG, Kee BS, Son HG, Ham BJ, Yang BH, Kim SH, et al. Genetic polymorphisms of alcohol and aldehyde dehydrogenase, dopamine and serotonin transporters in familial and non-familial alcoholism. Eur Neuropsychopharmacol. 2006;16:123–128.
Uchimoto T, Itoga S, Nezu M, Sunaga M, Tomonaga T, Nomura F. Role of the genetic polymorphisms in the 5'-flanking region for transcriptional regulation of the human CYP2E1 gene. Alcohol Clin Exp Res. 2007;31(1 Suppl):S36–42.
Hayashi S, Watanabe J, Kawajiri K. Genetic polymorphisms in the 50- flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem. 1991;110:559–565.
Babor TF, Higgins-Biddle JC, Saunders JB, Monteiro MG. AUDIT. Ginebra: Organización Mundial de la Salud. Departamento de Salud Mental y Dependencia de Sustancias; 2001.
Xu YL, Carr LG, Bosron WF, Li TK, Edenberg HJ. Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification. Genomics. 1988;2(3):209–214.
Raymond M, Rousset F. GENEPOP (Version 1.22): Population Genetics Software for Exact Tests and Ecumenicism. J Hered. 1995;86(3):248–249.
Rubio BN, Bermejo VJ, Caballero SM, Santo Domingo CJ. Validation of the alcohol use disorders identification test (AUDIT) in primary care. Madrid: Departamento de Psiquiatría, Universidad Autónoma de Madrid; 2000.
Hiraki M, Hiraki A, Hirose K, Ito H, Suzuki T, Wakai K, et al. Impact of the alcohol-dehydrogenase (ADH) 1C and ADH1B polymorphisms on drinking behavior in nonalcoholic Japanese. Hum Mutat. 2007;28:506–510.
Oyama T, Kawamato T, Mizoue T, Sugio K, Kodama Y, Mitsudomi T, et al. Cytochrome P4502E1 polymorphism as a risk factor for lung cancer: in relation to p53 gene mutation. Anticancer Res. 1997;1:583–588.
Wu X, Shi H, Jiang H, Kemp B, Hong WK, Delclos GL, et al. Associations between cytochrome P4502E1 genotype, mutagen sensitivity, cigarette smoking and susceptibility to lung cancer. Carcinogenesis. 1997;18:967–973.
Ulusoy G, Arinç E, Adali O. Genotype and allele frequencies of polymorphic CYP2E1in the Turkish population. Arch Toxicol. 2007;81:711–718.
Lorenzo A, Auguet T, Vidal F, Broch M, Olona M, Gutiérrez C, et al. Polymorphisms of alcohol metabolizing enzymes and the risk for alcoholism and alcoholic liver disease in Caucasian Spanish women. Drug Alcohol Depend. 2006;84:195–200.
Cichoz-Lach H, Celinski K, Slomka M. Alcohol-metabolizing enzyme gene polymorphisms and alcohol chronic pancreatitis among Polish individuals. HPB (Oxford) 2008;10:138–143.
Chen YC, Peng GS, Wang MF, Tsao TP, Yin SJ. Polymorphism of ethanol-metabolism genes and alcoholism: Correlation of allelic variations with the pharmacokinetic and pharmacodynamic consequences. Chem Biol Interact. 2009;178:2–7.
Peng G, Chen Y, Tsao TP, Wang MF, Yin SJ. Pharmacokinetic and pharmacodynamic basis for partial protection against alcoholism in Asians, heterozygous for the variant ALDH2*2 gene allele. Pharmacogenet Genomics. 2007;17:845–855.
OMS . Neurociencia del consumo y dependencia de sustancias psicoactivas. Ginebra: World Health Organization; 2004. http://www.who.int/substance_abuse/publications/neuroscience_spanish.pdf.
Chhabra SK, Reed CD, Anderson LM, Shiao YH. Comparison of the polymorphic regions of the cytochrome P450 CYP2E1 gene of humans and patas and cynomolgus monkeys. Carcinogenesis. 1999;20:1031–1034.
Walker SJ1.Grant KA.Vrana KE Examination of a CYP2E1 repeat polymorphism in a monkey model of alcohol abuse. Alcohol Clin Exp Res. 2001;25:1114–1118.
Rey M, Gutiérrez A, Schroeder B, Usaquén W, Carracedo A, Bustos I, et al. Allele frequencies for 13 STR's from two Colombian populations: Bogotá and Boyacá Forensic Sci Int. 2003;136:83–85.
Castro MTX, Aristizabal GFA, Rey BM. Determination of genetic polymorphism TaqIA (ANKK1) TaqIB (DRD2), -141c Ins/Del (DRD2) and 40 Bp VNTR (SLC6A3) in the Colombian population and evaluation of their associations with alcoholism. J Subst Abuse Alcohol. 2015;3:1039–1048.
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