skip to main content

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.

Citation Format:
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.

Note: This article has supplementary file(s).

Fulltext View|Download |  common.other
Covering Letter
Subject
Type Other
  Download (33KB)    Indexing metadata
Keywords: Non-alcoholic fatty liver disease; adiponectin; adiponutrin; Indonesia
Funding: Faculty of Medicine Diponegoro University under contract No.46/UN7.5.4/HK/2018

Article Metrics:

  1. Purnomo H, Mundhofir FEP, Kasno, Sudijanto E, Darmono, Daldiyono, et al. TNF - α Gene Polymorphism is Likely to be a Risk Factor for NASH in Indonesia. Hiroshima J Med Sci. 2018;67(6):101–9
  2. Agrawal S, Duseja AK. Non-alcoholic Fatty Liver Disease: East Versus West. J Clin Exp Hepatol. 2012;2(2):122–34
  3. Li H-J, Li C-P, Zhang C, Zhong X-L, Shi L. Association of Adiponectin gene polymorphisms and nonalcoholic fatty liver disease. Int J Clin Exp Med. 2015;8(9):16676–81
  4. Li X-L, Sui J-Q, Lu L-L, Zhang N-N, Xu X, Dong Q-Y, et al. Gene polymorphisms associated with non-alcoholic fatty liver disease and coronary artery disease: a concise review. Lipids Health Dis. 2016 Dec 10;15(1):53
  5. Dongiovanni P, Anstee QM, Valenti L. Genetic predisposition in NAFLD and NASH: impact on severity of liver disease and response to treatment. Curr Pharm Des. 2013;19(29):5219–38
  6. Lim JW, Dillon J, Miller M. Proteomic and genomic studies of non-alcoholic fatty liver disease--clues in the pathogenesis. World J Gastroenterol. 2014 Jul 14;20(26):8325–40
  7. Mishra A, Younossi ZM, Beatty G. Epidemiology and Natural History of Non-alcoholic Fatty Liver Disease. NAFLD Semin J Clin Exp Hepatol Ina J Clin Exp Hepatol. 2012;2(2):135–44
  8. Rastogi A, Shasthry SM, Agarwal A, Bihari C, Jain P, Jindal A, et al. Non-alcoholic fatty liver disease – histological scoring systems : a large cohort single-center, evaluation study. 2017;962–73
  9. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;1–11
  10. Sookoian S, Pirola CJ. Genetic predisposition in nonalcoholic fatty liver disease. Clin Mol Hepatol. 2017;23:1–12
  11. Umano G, Martino M, Santoro N. The Association between Pediatric NAFLD and Common Genetic Variants. Children. 2017;4(6):49
  12. Saki S, Saki N, Poustchi H, Malekzadeh R. Assessment of Genetic Aspects of Non-alcoholic Fatty Liver and Premature Cardiovascular Events. Middle East J Dig Diseaes. 2020;12(2):65–88
  13. Chen LZ, Xin YN, Geng N, Jiang M, Zhang DD, Xuan SY. PNPLA3 I148M variant in nonalcoholic fatty liver disease: Demographic and ethnic characteristics and the role of the variant in nonalcoholic fatty liver fibrosis. World J Gastroenterol. 2015 Jan 21;21(3):794–802
  14. Polyzos SA, Kountouras J, Mantzoros CS. Adipokines in nonalcoholic fatty liver disease. Metabolism. 2016 Aug 1;65(8):1062–79
  15. Purnomo HD, Kasno, Sudijanto E, Hirlan, Damono, Daldiyono, et al. The Roles of Metabolic Syndrome and Several Biomarkers in Incidence and Severity of Non Alcoholic Fatty Liver Disease. Hiroshima J Med Sci. 2018;67(4):138–46
  16. Flechtner-Mors M, George SN, Oeztuerk S, Haenle MM, Koenig W, Imhof A, et al. Association of adiponectin with hepatic steatosis: a study of 1,349 subjects in a random population sample. BMC Res Notes. 2014;7:207
  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
  18. Wang B-YYB-FF, Wang Y, Ao R, Tong J, Wang B-YYB-FF. AdipoQ T45 G and G276 T Polymorphisms and Susceptibility to Nonalcoholic Fatty Liver Disease Among Asian Populations: A Meta-Analysis and Meta-Regression. J Clin Lab Anal. 2016 Jan;30(1):47–57
  19. Zhou YJ, Zhang ZS, Nie YQ, Cao J, Cao CY, Li YY. Association of adiponectin gene variation with progression of nonalcoholic fatty liver disease: A 4-year follow-up survey. J Dig Dis. 2015;16(10):601–9
  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
  22. rs2241767 (SNP) - Explore this variant - Homo_sapiens - Ensembl genome browser 104 [Internet]. [cited 2021 Jun 24]. Available from: http://asia.ensembl.org/Homo_sapiens/Variation/Explore?r=3:186852907-186853907;v=rs2241767;vdb=variation;vf=91832562
  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

Last update:

No citation recorded.

Last update: 2021-11-30 05:01:33

No citation recorded.