Genetic polymorphism of ALDH2 in Indonesia’s Minang ethnic

  • Abdul Halim Sadikin Departement of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Irene Dian Departement of Biology, Faculty of Mathematics and Natural Sciences, State Jakarta University, Jakarta
  • Mukharjon Mukharjon Departement of Internal Medicine, Faculty of Medicine, Universitas Riau, Riau
  • Rini Puspitaningtum Departement of Biology, Faculty of Mathematics and Natural Sciences, State Jakarta University, Jakarta
  • Septelia Inawati Wanandi Departement of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta https://orcid.org/0000-0002-7963-8853
Keywords: ALDH2, alcohol, Minangkabau, polymorphism

Abstract

Background: In some people, acetaldehyde, a toxic product from ethanol oxidation, cannot be oxidized to acetate. The excess of acetaldehyde could cause facial flushing, dizziness, and hypertension when they consume ethanol. This ethanol sensitivity is caused by a deficiency of ALDH2.

Objective: This study aims to analyze and count the polymorphism frequency of the ALDH2 gene in Indonesia’s Minang ethnic.

Methods: DNA samples were taken randomly from hair bulbous of 60 subjects (male and female, 3rd generation). A nested polymerase chain reaction was conducted to amplify the ALDH2 in the samples. Afterward, restriction fragment length polymorphism (RFLP) was conducted to the amplicons using the EcoRI restriction enzyme. The measured parameters were the distribution of the wildtype, atypical homozygote, and heterozygote.

Results: Results showed that out of 60 subjects, 53.33% have an atypical homozygote gene (subjects prone to hypersensitive to alcohol), 28.33% have a heterozygote gene, and 18.33% have a wildtype gene. The frequency of the atypical alleles in Minang ethnic is 0.675.

Conclusion: The atypical ALDH2 allele was much higher than the normal ALDH2 allele, in which most participants have atypical homozygote ALDH2, suggesting the samples are sensitive to alcohol.

References

Mackus M, Loo AJ van de, Garssen J, Kraneveld AD, Scholey A, Verster JC. The role of alcohol metabolism in the pathology of alcohol hangover. J Clin Med. 2020;9. https://doi.org/10.3390/jcm9113421

Lee JH, Seo HJ, Cho S, Kim M-Y, Lee SD. Single Nucleotide Polymorphisms Associated with Alcohol-Induced Flushing Syndrome in Korean Population. Korean J Leg Med. 2019;43: 71. https://doi.org/10.7580/kjlm.2019.43.2.71

Jiang Y, Zhang T, Kusumanchi P, Han S, Yang Z, Liangpunsakul S. Alcohol Metabolizing Enzymes, Microsomal Ethanol Oxidizing System, Cytochrome P450 2E1, Catalase, and Aldehyde Dehydrogenase in Alcohol-Associated Liver Disease. Biomedicines. 2020;8. https://doi.org/10.3390/biomedicines8030050

Crabb DW, Matsumoto M, Chang D, You M. Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc Nutr Soc. 2004;63: 49-63. https://doi.org/10.1079/PNS2003327

Yokoyama A, Yokoyama T, Kimura M, Matsushita S, Yokoyama M. Combinations of alcohol-induced flushing with genetic polymorphisms of alcohol and aldehyde dehydrogenases and the risk of alcohol dependence in Japanese men and women. PLoS One. 2021;16: e0255276. https://doi.org/10.1371/journal.pone.0255276

Chen C-H, Cruz LA, Mochly-Rosen D. Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo. Proc Natl Acad Sci USA. 2015;112: 3074-3079. https://doi.org/10.1073/pnas.1414657112

Peng G-S, Chen Y-C, Wang M-F, Lai C-L, Yin S-J. ALDH2*2 but not ADH1B*2 is a causative variant gene allele for Asian alcohol flushing after a low-dose challenge: correlation of the pharmacokinetic and pharmacodynamic findings. Pharmacogenet Genomics. 2014;24: 607-617. https://doi.org/10.1097/FPC.0000000000000096

Edenberg HJ, McClintick JN. Alcohol dehydrogenases, aldehyde dehydrogenases, and alcohol use disorders: A critical review. Alcohol Clin Exp Res. 2018;42: 2281-2297. https://doi.org/10.1111/acer.13904

Shibuya A, Yoshida A. Genotypes of alcohol-metabolizing enzymes in Japanese with alcohol liver diseases: a strong association of the usual Caucasian-type aldehyde dehydrogenase gene (ALDH1(2)) with the disease. Am J Hum Genet. 1988;43: 744-748.

Goedde HW, Agarwal DP, Harada S. Genetic studies on alcohol-metabolizing enzymes: detection of isozymes in human hair roots. Enzyme. 1980;25: 281-286. https://doi.org/10.1159/000459265

Wanandi SI. Distribution of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) in Indonesian subjects. Med J Indones. 2002; 135. https://doi.org/10.13181/mji.v11i3.62

Simanjuntak T. The western route migration: A second probable neolithic diffusion to indonesia. In: Piper P, Matsumura H, Bulbeck D, editors. New perspectives in southeast asian and pacific prehistory. ANU Press; 2017. pp. 201-211. https://doi.org/10.22459/TA45.03.2017.11

Morimoto K, Takeshita T. Low Km aldehyde dehydrogenase (ALDH2) polymorphism, alcohol-drinking behavior, and chromosome alterations in peripheral lymphocytes. Environ Health Perspect. 1996;104 Suppl 3: 563-567. https://doi.org/10.1289/ehp.96104s3563

Agarwal DP. Genetic polymorphisms of alcohol metabolizing enzymes. Pathol Biol. 2001;49: 703-709. https://doi.org/10.1016/S0369-8114(01)00242-5

Chiang C-P, Jao S-W, Lee S-P, Chen P-C, Chung C-C, Lee S-L, et al. Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer. Alcohol. 2012;46: 37-49. https://doi.org/10.1016/j.alcohol.2011.08.004

Han H, Wang H, Yin Z, Jiang H, Fang M, Han J. Association of genetic polymorphisms in ADH and ALDH2 with risk of coronary artery disease and myocardial infarction: a meta-analysis. Gene. 2013;526: 134-141. https://doi.org/10.1016/j.gene.2013.05.002

Isomura M, Wang T, Yamasaki M, Hasan MZ, Shiwaku K, Nabika T. Aldehyde Dehydrogenase Polymorphisms and Blood Pressure Elevation in the Japanese: A Cross-Sectional and a Longitudinal Study over 20 Years in the Shimane CoHRE Study. Dis Markers. 2015;2015: 825435. https://doi.org/10.1155/2015/825435

Published
2021-12-07
How to Cite
Sadikin, A. H., Dian, I., Mukharjon, M., Puspitaningtum, R., & Wanandi, S. I. (2021). Genetic polymorphism of ALDH2 in Indonesia’s Minang ethnic. Acta Biochimica Indonesiana, 4(2), 14. https://doi.org/10.32889/actabioina.14