DOI: https://doi.org/10.14710/jbtr.v7i2.11777

Adiponutrin and Adiponectin Gene Variants in Indonesian Patients with Non-Alcoholic Fatty Liver Disease: a Preliminary Study

Faculty of Medicine, Universitas Diponegoro, Indonesia

Received: 20 Jul 2021; Revised: 27 Aug 2021; Accepted: 29 Aug 2021; Available online: 31 Aug 2021; Published: 31 Aug 2021.
Open Access Copyright (c) 2021 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

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Abstract

Background

Variants of adiponutrin (PNPLA3) and adiponectin (ADIPOQ) genes were considered to be associated with non-alcoholic fatty liver disease (NAFLD). Although the prevalence of NAFLD is increasing, there are limited numbers of studies about the association in Indonesian population.

Objective

To confirm whether specific variants of adiponutrin (PNPLA3) and adiponectin (ADIPOQ) genes are associated with NAFLD in Indonesian patients.

Methods

Data and DNA of 152 participants were obtained from a previous study in Dr. Kariadi Hospital, Semarang, Indonesia. PCR-RFLP analysis was performed for detection of PNPLA3 rs738409 and ADIPOQ rs2241767 variants. The diagnosis and severity of NAFLD were assessed according to NAFLD activity score (NAS) based on histopathology assessment of liverbiopsy.

Results

Allele G of PNPLA3rs738409 was associated with NAFLD in both bivariate (p=0.009, OR 2.52, CI 95% 1.25–5.07) and multivariate (p=0.008, OR 2.62, CI 95% 1.29%–5.32%) analysis, while ADIPOQ rs2241767 had no significant association. In NAFLD participants, both genotypes showed allele G was higher in the group of possible non-alcoholic steatohepatitis (NASH) – NASH (NAS >2) than in the simple steatosis group (NAS <2) i.e. 40.0% vs. 3.75% for the rs2241767 variant and 23.75% vs. 1.25% for the rs738409 variant, without significant association.

Conclusion

Variant PNPLA3 rs738409 was associated with NAFLD incidence in studied population. Among NAFLD participants, the frequency of both variants were found higher in the possible NASH – NASH group, yet needs to be confirmed with more participants and a multicenter study.
Data and DNA of 152 participants were obtained from a previous study in Dr. Kariadi Hospital, Semarang, Indonesia. PCR-RFLP analysis was performed for detection of PNPLA3 rs738409 and ADIPOQ rs2241767 variants. The diagnosis and severity of NAFLD were assessed according to NAFLD activity score (NAS) based on histopathology assessment of liverbiopsy.

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Keywords: Non-alcoholic fatty liver disease; adiponectin; adiponutrin; Indonesia
Funding: Faculty of Medicine Diponegoro University under contract No.46/UN7.5.4/HK/2018

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Language : EN
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  17. Abenavoli L, Milic N, Di Renzo L, Preveden T, Medić-Stojanoska M, De Lorenzo A. Metabolic aspects of adult patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2016 Aug 21;22(31):7006–16
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  20. Kleiner DE, Brunt EM. Nonalcoholic Fatty Liver Disease: Pathologic Patterns and Biopsy Evaluation in Clinical Research. Semin Liver Dis. 2012;32(01):003–13
  21. Islek EE, Sazci A, Ozel MD, Aygun C. Genetic variants in the PNPLA3 gene are associated with nonalcoholic steatohepatitis. Genet Test Mol Biomarkers. 2014;18(7):489–96
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  23. Hubé F, Glazko G, Rose AB. Introns as Gene Regulators: A Brick on the Accelerator. Front Genet. 2019;9(672)
  24. Valenti L, Rametta R, Ruscica M, Dongiovanni P, Steffani L, Motta BM, et al. The I148M PNPLA3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls. BMC Gastroenterol. 2012 Aug 16;12:111
  25. Pingitore P, Romeo S. The role of PNPLA3 in health and disease. BBA - Mol Cell Biol Lipids. 2018;1864(6):900–6
  26. Abd El-Kader SM, El-Den Ashmawy EMS. Non-alcoholic fatty liver disease: The diagnosis and management. World J Hepatol. 2015 Apr 28;7(6):846–58
  27. Thandra KC, Barsouk A, Saginala K, Aluru JS, Rawla P, Barsouk A. Epidemiology of non-alcoholic fatty liver disease and risk of hepatocellular carcinoma progression. Vol. 6, Clinical and Experimental Hepatology. Termedia Publishing House Ltd.; 2021. p. 289–94
  28. Dai G, Liu P, Li X, Zhou X, He S. Association between PNPLA3 rs738409 polymorphism and nonalcoholic fatty liver disease (NAFLD) susceptibility and severity: A meta-analysis. Med (United States). 2019;98(7)
  29. Li J, Hua W, Ji C, Rui J, Zhao Y, Xie C, et al. Effect of the patatin-like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta-analysis of paediatric and adolescent individuals. Pediatr Obes. 2020 Jun 1;15(6)
  30. Xu R, Tao A, Zhang S, Deng Y, Chen G. Association Between Patatin-Like Phospholipase Domain Containing 3 Gene (PNPLA3) Polymorphisms and Nonalcoholic Fatty Liver Disease: A HuGE Review and Meta-Analysis. Sci Rep. 2015 Aug 20;5(1):9284
  31. Salameh H, Hanayneh M Al, Masadeh M, Naseemuddin M, Matin T, Erwin A, et al. PNPLA3 as a genetic determinant of risk for and severity of non-alcoholic fatty liver disease spectrum. J Clin Transl Hepatol. 2016;4(3):175–91

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