Skip to main content
  • Original article
  • Open access
  • Published:

Detection of patatin-like phospholipase domain-containing protein 3 in nonalcoholic fatty liver disease among egyptian patients

En

Abstract

Background and aim

Recently, studies have identified patain-like phospholipase domain containing 3 (PNPLA3), which is localized in the endoplasmic reticulum and at the surface of lipid droplets. The association of PNPLA3 polymorphisms with fatty liver and histological severity of NAFLD was shown in many studies. We aimed to investigate the association of PNPLA3 with the development and severity of NAFLD in an overweight and obese Egyptian population.

Patients and methods

Eighty overweight and obese patients with NAFLD were enrolled in the study. Patients were divided into 2 subgroups according to results of liver biopsy: group 1 included 30 patients with simple steatosis, and group 2 included 50 patients with non-alcoholic steatohepatitis (NASH). In addition to 10 age-matched healthy subjects served as a control group. All NAFLD patients underwent a confirmatory biopsy. Laboratory investigations included fasting glucose, liver enzymes and lipid profile were done. Abdominal ultrasound was performed and PNPLA3 was detected in each patient by Quantitative ELISA.

Results

Levels of PNPLA3 were higher in NAFLD patients compared with controls (85.70±76.42 vs 3.10±2.11 respectively) and levels were also higher in NASH than simple steatosis (125.09±71.78 vs 20.06±8.47 vs 3.10±2.11 respectively, P<0.001). There were highly significant positive correlations between the PNPLA3 and waist circumference, BMI, ALT, AST, total cholesterol and TGs in the NAFLD patients.

Conclusions

Our study confirmed the association of PNPLA3 with the incidence of NAFLD and progression to NASH in the Egyptian patients.

References

  1. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001; 50: 1844–1850.

    Article  CAS  Google Scholar 

  2. Wilfred de Alwis NM, Day CP. Genes and nonalcoholic fatty liver disease. Curr Diab Rep 2008; 8:156–163.

    Article  Google Scholar 

  3. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461–1465.

    Article  CAS  Google Scholar 

  4. Sookoian S, Castano GO, Burgueno AL, Gianotti TF, Rosselli MS, Pirola CJ. A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J Lipid Res 2009; 50: 2111–2116.

    Article  CAS  Google Scholar 

  5. Sookoian S, Pirola CJ. Metabolic syndrome: from the genetics to the pathophysiology. Curr Hypertens Rep 2011; 13: 149–157.

    Article  CAS  Google Scholar 

  6. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013; 310:2191–2194.

    Article  Google Scholar 

  7. Ricci C, Longo R, Gioulis E, Bosco M, Pollesello P, Masutti F et al. Noninvasive in vivo quantitative assessment of fat in human liver. J Hepatol 1997; 27: 108–113.

    Article  CAS  Google Scholar 

  8. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55: 2005–2023.

    Article  Google Scholar 

  9. Mohamed AA, Gohary KKE, Mashad GME, Hammoda GE, Abdallah AM, Khattab RA et al. Interleukin 10, thyroid status and ferritin are non-invasive prognostic biomarkers for diagnosis of fatty liver disease in children. J Int Res Med Pharma Sci 2016; 8: 85–93.

    Google Scholar 

  10. Day CP, James OF. Steatohepatitis: a tale of two ‘hits’? Gastroenterology 1998; 114: 842–845.

    Article  CAS  Google Scholar 

  11. Mahmoud HS, Helal MM, Hassan MH, Sherif MF. Correlation between anthropometric measures, lipid profile and serum adiponectin and steatosis in nondiabetic nonalcoholic fatty liver disease. Br J Med Medi Res 2015; 7: 771–778.

    Article  Google Scholar 

  12. Hegazy MA, Samie RMA, Ezzat A, Ramadan N, Rashed LA, ElSayed AM. PNPLA3 and TNF-α G238A genetic polymorphisms in Egyptian patients with different grades of severity of NAFLD. Open J Gastroenterol 2016; 6: 53–64.

    Article  CAS  Google Scholar 

  13. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R et al. Non alcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003; 37: 917–923.

    Article  Google Scholar 

  14. Clark JM, Diehl AM. Nonalcoholic fatty liver disease: anunder-recognized cause of cryptogenic cirrhosis. JAMA 2003; 289: 3000–3004.

    Article  Google Scholar 

  15. Harnois F, Msika S, Sabaté JM, Mechler C, Jouet P, Barge J et al. Prevalence and predictive factors of NASH in morbidly obese patients undergoing bariatric surgery. Obes Surg 2006; 16: 183–188.

    Article  Google Scholar 

  16. Caldwell SH, Argo CK. Non-alcoholic fatty liver disease and nutrition. In: Dooley, et al. Sherlock’s diseases of the liver and biliary system 12th Edition. Oxford: Blackwell Publishing Ltd; 2011. 28:546–561.

    Chapter  Google Scholar 

  17. Kim HC, Choi SH, Shin HW, Cheong JY, Lee KW, Lee HC et al. Severity of ultrasonographic liver steatosis and metabolic syndrome in Korean men and women. World J Gastroenterol 2005; 11: 5314–5321.

    Article  Google Scholar 

  18. Borai IH, Shaker Y, Kamal MM, Ezzat WM, Ashour E, Afify M et al. Evaluation of biomarkers in egyptian patients with different grades of nonalcoholic fatty liver disease. J Clin Transl Hepatol 2017; 5: 109–118.

    Article  Google Scholar 

  19. Kim HJ, Kim HJ, Lee KE, Kim DJ, Kim SK, Ahn CW et al. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med 2004; 164: 2169–2175.

    Article  Google Scholar 

  20. Sorrentino P, Tarantino G, Conca P, Perrella A, Terracciano ML, Vecchione R et al. Silent non-alcoholic fatty liver disease a clinical-histological study. J Hepatol 2004; 41: 751–757.

    Article  CAS  Google Scholar 

  21. Amarapurkar D, Kamani P, Patel N, Gupte P, Kumar P, Agal S et al. Prevalence of non-alcoholic fatty liver disease: population based study. Ann Hepatol 2007; 6: 161–163.

    Article  Google Scholar 

  22. Duseja A, Das A, Das R, Dhiman RK, Chawla Y, Bhansali A et al. The clinicopathological profile of Indian patients with nonalcoholic fatty liver disease (NAFLD) is different from that in the west. Dig Dis Sci 2007; 52: 2368–2374.

    Article  Google Scholar 

  23. Arvaniti VA, Thomopoulos KC, Tsamandas A, Makri M, Psyrogiannis A, Vafiadis G et al. Serum adiponectin levels in different types of non-alcoholic liver disease. Correlation with steatosis, necroinflammation and fibrosis. Acta Gastroenterol Belg 2008; 71: 355–360.

    CAS  PubMed  Google Scholar 

  24. Shi JP, Xun YH, Hu CB, Zhang L, Liu H, Lou GQ et al. Clinical and histological features of non-alcoholic fatty liver disease. Zhonghua Gan Zang Bing Za Zhi 2009; 17: 812–816.

    CAS  PubMed  Google Scholar 

  25. Fracanzani AL, Valenti L, Bugianesi E, Vanni E, Grieco A, Miele L et al. Risk of nonalcoholic steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease and low visceral adiposity. J Hepatol 2011; 54: 1244–1249.

    Article  CAS  Google Scholar 

  26. Pulzi F, Cisternas R, Melo MR, Ribeiro CMF, Malheiros CA, Salles JE et al. New clinical score to diagnose non-alcoholic steatohepatitis in obese patients. Diabetol Metab Syndr 2011; 3: 3.

    Article  CAS  Google Scholar 

  27. Ong JP, Elariny H, Collantes R, Younoszai A, Chandhoke V, Reines HD et al. Predictors of non-alcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obes Surg 2005; 15: 310–315.

    Article  Google Scholar 

  28. Chan WK, Sthaneshwar P, Nik Mustapha NR, Mahadeva S. Limited utility of plasma M30 in discriminating non-alcoholic steatohepatitis from steatosis − a comparison with routine biochemical markers. PLoS One 2014; 9:e105903.

    Article  Google Scholar 

  29. Kashyap SR, Diab DL, Baker AR, Yerian L, Bajaj H, Gray-McGuire C et al. Triglyceride levels and not adipokine concentrations are closely related to severity of nonalcoholic fatty liver disease in an obesity surgery cohort. Obesity (Silver Spring) 2009; 17: 1696–1701.

    Article  CAS  Google Scholar 

  30. Assy N, Kaita K, Mymin D, Levy C, Rosser B, Minuk G. Fatty infiltration of liver in hyperlipidemic patients. Dig Dis Sci 2000; 45: 1929–1934.

    Article  CAS  Google Scholar 

  31. Chen CH, Huang MH, Yang JC, Nien CK, Yang CC, Yeh YH et al. Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of Taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults. J Clin Gastroenterol 2006; 40: 745–752.

    Article  CAS  Google Scholar 

  32. Paredes-Turrubiarte G, González-Chávez A, Pérez-Tamayo R, Salazar-Vázquez BY, Hernández VS, Garibay-Nieto N et al. Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients. Clin Exp Med 2016; 16: 193–202.

    Article  CAS  Google Scholar 

  33. Stickel F, Hampe J, Trépo E, Datz C, Romeo S. PNPLA3 genetic variation in alcoholic steatosis and liver disease progression. Hepatobiliary Surg Nutr 2015; 4: 152–160.

    PubMed  PubMed Central  Google Scholar 

  34. Aragonès G, Auguet T, Armengol S, Berlanga A, Guiu-Jurado E, Aguilar C et al. PNPLA3 expression is related to liver steatosis in morbidly obese women with non-alcoholic fatty liver disease. Int J Mol Sci 2016; 17: 630–643.

    Article  Google Scholar 

  35. Kotronen A, Johansson LE, Johansson LM, Roos C, Westerbacka J, Hamsten A et al. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia 2009; 52: 1056–1060.

    Article  CAS  Google Scholar 

  36. Trépo E, Romeo S, Zucman-rossi J, Nahon P. PNPLA3 gene in liver diseases. J Hepatol 2016; 65: 399–412.

    Article  Google Scholar 

  37. Kollerits B, Coassin S, Kiechl S, Hunt SC, Paulweber B, Willeit J et al. A common variant in the adiponutrin gene influences liver enzyme levels. J Med Genet 2010; 47: 116–119.

    Article  CAS  Google Scholar 

  38. Ruhanen H, Perttilä J, Hölttä-Vuori M, Zhou Y, Yki-Järvinen H, Ikonen E et al. PNPLA3 mediates hepatocyte triacylglycerol remodeling. J Lipid Res 2014; 55: 739–746.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mohamed O. Khalifa MD.

Additional information

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El Saeed, K.M., Ahmed, O.A., Khalifa, M.O. et al. Detection of patatin-like phospholipase domain-containing protein 3 in nonalcoholic fatty liver disease among egyptian patients. Egypt J Intern Med 31, 273–280 (2019). https://doi.org/10.4103/ejim.ejim_43_18

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/ejim.ejim_43_18

Keywords