First description and evaluation of SNPs in the ADH and ALDH genes in a population of alcoholics in Central-West Brazil

Abstract

Worldwide, different studies have reported an association of alcohol-use disorder (AUD) with different types of Single Nucleotide Polymorphisms (SNPs) in the genes for aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH). In Brazil, there is little information about the occurrence of these SNPs in the AUD population and an absence of studies characterizing the population in the Central-West Region of Brazil. Actually, in Brazil, there are more than 4 million people with AUD. Despite the major health hazards of AUD, information on alcohol consumption and its consequences are not well understood. Therefore, it is extremely important to characterize these SNPs for the better understanding of AUD as a genetic disease in the Brazilian population. The present study, unlike other studies in other countries, is done with a subject population that shows a significant amount of racial homogenization. We evaluated the presence of SNPs in the ADH (ADH1B, ADH1C, and ADH4) and ALDH (ALDH2) genes in alcohol users of Goiânia, State of Goiás - Brazil, and then we established a possible relationship with AUD by allelic and genotypic study. This study was conducted with a population of people with AUD (n = 99) from Goiás Alcohol Dependence Recovery Center (GO CEREA) and Psychosocial Care Center for Alcohol and Drugs (CAPS AD), and with a population of people without AUD as controls (n = 100). DNA was extracted from whole-blood samples and the genotyping was performed using TaqMan SNP genotyping assays. For characterization and evaluation of SNPs in the population, genotype frequency, allele frequency, haplotype frequency, Hardy-Weinberg equilibrium, and linkage disequilibrium were analyzed. Statistical analyses were calculated by GENEPOP 4.5 and Haploview software. The allele 1 was considered as "wild" (or *1) and allele 2 as mutant (or *2). Significant differences were found for ADH1B*, ADH4*2, and ALDH2*2 SNPs when the genotype and allele frequencies were analyzed. In addition, four haplotypes were observed between ADH1B*2 and ADH1C*2 through linkage disequilibrium analysis. The genetic variants may be associated with protection against AUD in the population studied.

Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review

“…Edenberg et al found significant associations between ADH4 rs1984362, rs4699718, rs3762894, rs4148886, rs4699714, rs7694646, rs1126672, DWSHpy188I, rs1042364, rs1042365, rs2602866, and rs2602846 and alcoholism [ 101 ]. The association of ADH4 rs1042364 was replicated in AUD patients from Central-West Brazil [ 102 ]. In addition, ADH4 rs1800759 was related to the early stages of metabolism, whereas ADH4 rs2032349 and rs1573495 were associated with the elimination rate [ 97 ].…”

Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

“…5 Throughout the past decades, pioneering studies support that the aberrant expression of ALDHs is related to several human non-tumor diseases, for example, Alzheimer's disease (AD) 6 and alcohol intolerance, 7 which are caused by the loss of activity or deficiency of enzyme expression and accumulation of toxic aldehydes. Another ALDH-related disorder is caused by ALDH gene mutations, especially single-nucleotide polymorphisms, 8 contributing to enzyme inactivation, cellular dysfunction, interruption of normal metabolic pathways, and susceptibility to human diseases, such as Sjögren-Larsson syndrome (SLS) and hyperprolinemia type II (HPII). Polymorphisms within these genes may differentially affect the risk of disease development across the ethnic groups evaluated.…”

Characteristic and influencing factors of Taqman genotyping calling error

“…There are many methods for SNP genotyping, including MALDI‐TOF mass spectrometry, Taqman probe, restriction fragment length polymorphism (RFLP), microarray, and DNA sequencing . Due to the high cost, MALDI‐TOF mass spectrometry, microarray, and DNA sequencing are not suitable for analysis of large samples.…”