PNPLA3 rs738409 polymorphism in Patients with Type 2 Diabetes and Concomitant Liver Pathology in Yakutia

Khariton A. Kurtanov, Nadezhda I. Pavlova, Aleksandra T. Diakonova, Lyubovy A. Sydykova, Sardana V. Markova, Vladimir V. Dodokhov

International Journal of Biomedicine. 2020;10(4):438-441.
DOI: 10.21103/Article10(4)_OA21
Originally published December 10, 2020


Background: The pathogenetic mechanisms of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) are closely related. Currently, multiple studies have demonstrated a link between the PNPLA3 148M variant and the development and progression of NAFLD, including liver fibrosis. The aim of our research was to study the distribution of alleles and genotypes of the PNPLA3 rs738409 SNP in Russians and Yakuts living in Yakutia, as well as to search for associations of the PNPLA3 rs738409 SNP in patients with T2D and non-alcoholic fatty liver disease / non-alcoholic steatohepatitis.
Methods and Results: The study included 179 patients (28 Russians and 151 Yakuts) with T2D and concomitant liver diseases of non-infectious origin. The comparison group consisted of 147 healthy volunteers of Russian ethnicity and 246 healthy volunteers of Yakut ethnicity. The PNPLA3 738409 SNP was analyzed by PCR-RFLP reaction. The results found a significant difference between the frequencies of the PNPLA3 rs738409 genotypes and alleles in Russians and Yakuts, both among healthy volunteers and in T2D patients with liver diseases. The frequency of the G allele occurrence in the group of healthy Yakuts was significantly higher (OR- 3.313; 95% CI: 2.444-4.499; P<0.001) than in the group of healthy Russians. No significant differences were found for the PNPLA3 rs738409 genotype and allele frequencies among a healthy sample and a sample of T2D patients with non-alcoholic fatty liver disease / non-alcoholic steatohepatitis, both in the Russian and Yakut populations.

type 2 diabetes • non-alcoholic fatty liver disease • PNPLA3 • rs738409 • I148M
  1. Birjukova EV, Rodionova S.V. [Type 2 diabetes and non-alcoholic fatty liver disease are modern diseases]. Medical almanac. 2017; 6 (51):130-135. [Article in Russian].
  2. Targher G, Byrne CD. Clinical Review: Nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications. J Clin Endocrinol Metab. 2013 Feb;98(2):483-95. doi: 10.1210/jc.2012-3093. 
  3. Petunina NA, Tel'nova MJe. [Non-alcoholic fatty liver disease]. Medical Council. 2016;4:92-95. [Article in Russian].
  4. Sharonova LA, Verbovoj AF, Verbovaja NI, Pashenceva AV. [Relationship between non-alcoholic fatty liver disease and type 2 diabetes]. Russian Medical Journal. 2017;22:1635-1640.5. [Article in Russian].
  5. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016 Aug;65(8):1038-48. doi: 10.1016/j.metabol.2015.12.012. 
  6. Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L. Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis. World J Gastroenterol. 2018 Aug 14;24(30):3361-3373. doi: 10.3748/wjg.v24.i30.3361.
  7. Marjot T, Moolla A, Cobbold JF, Hodson L, Tomlinson JW. Nonalcoholic Fatty Liver Disease in Adults: Current Concepts in Etiology, Outcomes, and Management. Endocr Rev. 2020 Jan 1;41(1):bnz009. doi: 10.1210/endrev/bnz009. 
  8. Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ. Characterization of the human patatin-like phospholipase family. J Lipid Res. 2006 Sep;47(9):1940-9. doi: 10.1194/jlr.M600185-JLR200.
  9. Kotronen A, Johansson LE, Johansson LM, Roos C, Westerbacka J, Hamsten A, Bergholm R, Arkkila P, Arola J, Kiviluoto T, Fisher RM, Ehrenborg E, Orho-Melander M, Ridderstråle M, Groop L, Yki-Järvinen H. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia. 2009 Jun;52(6):1056-60. doi: 10.1007/s00125-009-1285-z. 
  10. Huang Y, Cohen JC, Hobbs HH. Expression and characterization of a PNPLA3 protein isoform (I148M) associated with nonalcoholic fatty liver disease. J Biol Chem. 2011 Oct 28;286(43):37085-93. doi: 10.1074/jbc.M111.290114.
  11. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008 Dec;40(12):1461-5. doi: 10.1038/ng.257. 
  12. Rotman Y, Koh C, Zmuda JM, Kleiner DE, Liang TJ; NASH CRN. The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. Hepatology. 2010 Sep;52(3):894-903. doi: 10.1002/hep.23759. 
  13. Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology. 2011 Jun;53(6):1883-94. doi: 10.1002/hep.24283.
  14. Krawczyk M, Grünhage F, Zimmer V, Lammert F. Variant adiponutrin (PNPLA3) represents a common fibrosis risk gene: non-invasive elastography-based study in chronic liver disease. J Hepatol. 2011 Aug;55(2):299-306. doi: 10.1016/j.jhep.2010.10.042.
  15. Zain SM, Mohamed R, Mahadeva S, Cheah PL, Rampal S, Basu RC, Mohamed Z. A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease. Hum Genet. 2012 Jul;131(7):1145-52. doi: 10.1007/s00439-012-1141-y. 
  16. Dongiovanni P, Donati B, Fares R, Lombardi R, Mancina RM, Romeo S, Valenti L. PNPLA3 I148M polymorphism and progressive liver disease. World J Gastroenterol. 2013 Nov 7;19(41):6969-78. doi: 10.3748/wjg.v19.i41.6969.
  17. Chandrasekharan K, Alazawi W. Genetics of Non-Alcoholic Fatty Liver and Cardiovascular Disease: Implications for Therapy? Front Pharmacol. 2020 Jan 8;10:1413. doi: 10.3389/fphar.2019.01413.
  18. GSR and the 1000 Genomes Project [Internet]. Available from:

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Received October 26, 2020.
Accepted December 6, 2020.
©2020 International Medical Research and Development Corporation.