Alcohol dehydrogenase 1C (ADH1C) polymorphism is significantly associated with kidney function status in Nusa Tenggara Timur ethnicity: A cross-sectional study

https://doi.org/10.22146/jcoemph.61561

Budiatri Retno Noormaningrum(1*), Yudha Nurhantari(2), Suhartini Suhartini(3), Tri Ratnaningsih(4), Maria Agnes Etty Dedy(5)

(1) Department of Forensic and Legal Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta
(2) Department of Forensic and Legal Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta
(3) Department of Forensic and Legal Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta
(4) Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
(5) Department of Anesthesiology & Intensive care, General Hospital Prof.Dr. W.Z. Johannes Kupang / Faculty of Medicine, University of Nusa Cendana, Kupang
(*) Corresponding Author

Abstract


Excessive alcohol consumption is harmful to many human organs, but the association with kidney function is still controversial. The disagreement in findings might be caused by ADH1C polymorphism's influence on alcohol metabolism rate. This study aims to determine the correlation between ADH1C polymorphism and kidney function status in Nusa Tenggara Timur (NTT) ethnicity, a population with highly prevalent alcohol consumption in Indonesia. We conducted a cross-sectional study of 76 subjects, who are natives of NTT, Indonesia. The genotyping of extracted DNA for ADH1C was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using restriction endonuclease SspI. Kidney function status was defined by serum urea level and estimated glomerular filtration rate (eGFR) that had been categorized according to percentiles. The correlation with the ADH1C allele was analyzed using chi-square tests. The genotype of ADH1C in NTT ethnicity was ADH1C*1/*2 (51.3%), ADH1C*2/*2 (47.4%), and ADH1C*1/*1 (1.3%). The results showed that the population had the ADH1C*2 (73.03%) and the ADH1C*1 (26.97%) allele. There was a significant association between ADH1C polymorphism and eGFR among NTT ethnicity (p=0.005) when eGFR was analyzed at the 25th percentile (74.75 mL/minute/1.73m2). However, we found no associations when eGFR was analyzed at 50th (p=0.571) and 75th (p=0.335) percentiles. The odds ratio shows that having the ADH1C*1/*2 genotype escalates the probability of declining eGFR 6.620 times compared to ADH1C*2/*2 (95% CI: 1.539-28.478), after adjusted for smoking behavior. We found no association between ADH1C polymorphism and serum urea level (p=0.123, 0.421, and 0.335). The majority of NTT ethnicity have the ADH1C*1/*2 genotype. Populations with ADH1C*1/*2 have higher odds ratio for eGFR below 74.75 mL/minute/1.73m2 than those with ADH1C*2/*2 genotype. There was no association between ADH1C polymorphism and serum urea levels.


Keywords


ADH1C polymorphism; alcohol dehydrogenase; glomerular filtration rate

Full Text:

PDF


References

  1. Lassnigg A, Schmildlin D, Mouhieddine M, Bachmann LM, Druml W, Bauer P, et al. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: A prospective cohort study. J Am Soc Nephrol [Internet]. 2004 Jun 1;15(6):1597–605. Available from: http://www.jasn.org/cgi/doi/10.1097/01.ASN.0000130340.93930.DD
  2. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: A systematic review and meta-analysis. Kidney Int. 2012;81(5):442–8.
  3. BPJS. Laporan Pengelolaan Program and Laporan Keuangan Jaminan Sosial Kesehatan Tahun 2017 [Program Management and Financial Report of Social Health Insurance 2017]. 2017;150. Available from: https://bpjs-kesehatan.go.id/bpjs/dmdocuments/5b8c446214547b3f6727a710cd62dae7.pdf
  4. Hammer JH, Parent MC, Spiker DA, World Health Organization. Global Status Report on Alcohol and Health. 2018, Vol. 65, 74–85 p.
  5. Laporan Nasional Riskesdas [Internet]. Badan Penelitian dan Pengembangan Kesehatan. 2018. Available from: http://labdata.litbang.kemkes.go.id/images/download/laporan/RKD/2018/Laporan_Nasional_RKD2018_FINAL.pdf
  6. Salesman F, Juraman SR, Lette A, Gobang YGD, Rengga MPE. The controversy between the Indonesian government policy and Manggarai’s culture value about “sopi” liquor. J Drug Alcohol Res. 2018;7(74).
  7. Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, Brabec BA, O’corragain OA, Edmonds PJ, et al. High alcohol consumption and the risk of renal damage: A systematic review and meta-analysis. Qjm. 2015;108(7):539–48.
  8. Lin M, Su Q, Huang H, Zheng Y, Wen J, Yao J, et al. Alcohol consumption and the risk for renal hyperfiltration in the general Chinese population. Eur J Clin Nutr. 2017;71(4):500–5.
  9. Seitz HK, Mueller S. Alcohol: Metabolism, Toxicity and Its Impact on Nutrition. Third Edit. Reference Module in Biomedical Sciences. Elsevier; 2014. 1–13 p. Available from: https://www.sciencedirect.com/science/article/pii/B9780128012383002294
  10. Suhartini, Mustofa, Nurhantari Y, Rianto BUD. The analysis of polymorphism of Alcohol dehydrogenase 3 (ADH3) gene and influence of liver function status in Indonesia. Kobe J Med Sci. 2016;62(4):E107–13.
  11. Priyambodo DY. Hubungan antara Polimorfisme Gen ADH3 dengan Perilaku Minum Alkohol pada Mahasiswa Papua di Yogyakarta [master thesis]. Universitas Gadjah Mada; 2018.
  12. Cox MP, Karafet TM, Lansing JS, Sudoyo H, Hammer MF. Autosomal and X-linked single nucleotide polymorphisms reveal a steep Asian-Melanesian ancestry cline in eastern Indonesia and a sex bias in admixture rates. Proc R Soc B Biol Sci. 2010;277(1687):1589–96.
  13. Latella MC, Di Castelnuovo A, de Lorgeril M, Arnout J, Cappuccio FP, et al. Genetic variation of alcohol dehydrogenase type 1C (ADH1C), alcohol consumption, and metabolic cardiovascular risk factors: Results from the IMMIDIET study. Atherosclerosis. 2009;207(1):284–90.
  14. Shen Y, Fan J, Edenberg HJ, Li T, Cui Y, Wang Y, et al. Polymorphism of ADH and ALDH genes among four ethnic groups in China and effects upon the risk for alcoholism. Alcohol Clin Exp Res. 1997;21(7):1272–7.
  15. Relethford JH. Human Population Genetics, First Edition. In Wiley & Sons, Inc.; 2012. p. 23–48.
  16. Van Der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey A, et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int [Internet]. 2011;79(12):1341–52. Available from: http://dx.doi.org/10.1038/ki.2010.536
  17. Dasgupta A. Genetic aspects of alcohol metabolism and drinking behavior. In Alcohol: Its Biomarkers. 2015;37–63.
  18. Edenberg HJ. The genetics of alcohol metabolism: Role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res Heal. 2007;30(1):5–13.
  19. Singh D, Negi TS, Upadhya G, Choudhuri G. Polymorphism of alcohol metabolizing gene ADH3 predisposes to development of alcoholic pancreatitis in North Indian population. Front Mol Biosci. 2015;2(DEC):1–6.
  20. Terry MB, Gammon MD, Zhang FF, Knight JA, Wang Q, Britton JA, et al. ADH3 genotype, alcohol intake and breast cancer risk. Carcinogenesis. 2006;27(4):840–7.
  21. Wang X, Vrtiska TJ, Avula RT, Walters LR, Chakkera HA, Kremers WK, et al. Age, kidney function, and risk factors associate differently with cortical and medullary volumes of the kidney. Kidney Int. 2014;85(3):677–85.
  22. Yoon YE, Lee HH, Na JC, Huh KH, Kim MS, Kim SI, Han WK. Impact of cigarette smoking on living kidney donors. Transplant Proc. 2018;50(4):1029–33.
  23. Leal S, Ricardo Jorge DO, Joana B, Maria SS, Isabel SS. Heavy alcohol consumption effects on blood pressure and on kidney structure persist after long-term withdrawal. Kidney Blood Press Res. 2017;42(4):664–75.
  24. Suhartini, Widagdo H, Wira Agni IA, Nurhantari Y. The analysis of cell damage of liver and kidney among alcoholics in Yogyakarta, Indonesia. J Med Sci (Berkala Ilmu Kedokteran). 2019;51(03):246–57.
  25. Lamb EJ, Jones GRD. 32 - Kidney Function Tests. In: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics [Internet]. Sixth Edit. Elsevier Inc.; 2020. p. 479-517.e16. Available from: http://dx.doi.org/10.1016/B978-0-323-35921-4.00032-6



DOI: https://doi.org/10.22146/jcoemph.61561

Article Metrics

Abstract views : 453 | views : 293

Refbacks

  • There are currently no refbacks.


Copyright (c) 2021 Journal of Community Empowerment for Health

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.