HEPATOCYTES' FUNCTION AND ADIPOKINES IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE DEPENDING ON THE ACE (rs4646994) AND PPAR-2 (rs1801282) GENES' POLYMORPHISMS
Non-alcoholic fatty liver disease (NAFLD) is a pathology characterized by accumulation of fat (steatosis) found in at least 5% of hepatocytes, and is a multifactorial disease including a genetic component. Aim: To analyze the association of polymorphism of the ACE (I/D) and PPAR-g2 (Pro12Ala) genes with functional activity of hepatocytes and adipocytokines content in patients with NAFLD. Material and methods: The study involved 96 patients with NAFLD and obesity (OB): men-41.67%, women-58.33%. Liver function was studied by the activity of organ-specific enzymes. The polymorphisms of PPAR-g2 (Pro12Ala) and ACE (I/D) genes were studied by PCR. Results: The leptin plasma level was 1.74-2.39 times higher in women compared to men with development of leptin resistance (LR) regardless of NAFLD type or OB degree, especially in the D-allele of the ACE gene carriers by 22.19% and 28.73%. Conclusions: This study shows existing associations of changes in hepatic function, lipid metabolism, and adipocytokines activity in NAFLD with the ACE (rs4646994) and PPAR-g2 (rs1801282) genetic polymorphisms. ACE DD-genotype and PPAR-g2 gene's Ala-allele associate with higher conjugated bilirubin, transaminases, and leucocytes. Secretory activity of adipose tissue is significantly higher by the content of pro-atherogenic leptin, with the development of leptin resistance in women, regardless of the NAFLD type and OB degrees, especially in D-allele carriers of the ACE gene. NAFLD with OB is characterized by reliable increase in leptin concentration, especially in Pro12 genotype carriers of the PPAR-g2 gene, with increase in LR and decrease of anti-atherogenic adiponectin.
2. Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol 2015; 62: 47-64.
3. Sydorchuk LP, Sokolenko AA, Sydorchuk AR et al. Insulin resistance in patients with arterial hyper-tension and abdominal obesity depending on ACE and PPAR-γ2 genes polymorphism: a new opinion concerning an old problem. The New Armenian Med J 2015; 9(2): 43-51.
4. Petta S, Gastaldelli A, Rebelos E et al. Pathophysiology of nonalcoholic fatty liver disease. Lonardo A, Targher G, eds. Int J Mol Sci 2016; 17(12): 2082.
5. Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science 2011; 332(6037): 1519-1523.
6. Polyzos SA, Aronis KN, Kountouras J, Raptis DD, Vasiloglou MF, Mantzoros CS. Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Diabetologia 2016; 59(1): 30-43.
7. Yarynych YuM, Sydorchuk LP. Combined influence of polymorphic variants of PPAR-γ2 (rs1801282) and ACE (rs4646994) genes on the onset of non-alcoholic fatty liver disease in patients with essential arterial hypertension and obesity. J Education, Health and Sport 2018; 8(2): 364-371.
8. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatology 2016; 64(6): 1388-1402.
9. Sidorchuk R. Laser polarimetry of conjuctive biotissue. Proceedings of SPIE 2002; 4705: 200-210.
10. Fargion S, Porzio M, Fracanzani AL. Nonalcoholic fatty liver disease and vascular disease: state-of-the-art. World J Gastroenterol 2014; 20(37): 13306-13324.
11. Burt VL, Harris T. The Third National Health and Nutrition Examination Survey: Contributing Data on Aging and Health. The Gerontologist 1994; 34(4): 486-490.
12. Sydorchuk LP, Gaborec IY, Sydorchuk AR et al. Combined effects of ACE (I/D) and eNOS (894T>G) genes polymorphism in patients with arterial hypertension in the realization of molecular mechanisms of left ventricular hypertrophy. The New Armenian Med J 2013; 7(2): 44-54.
13. Eslam M, Valenti L, Romeo S. Genetics and epigenetics of NAFLD and NASH: Clinical impact. J Hepatology 2018; 68(2): 268-279.
14. Sookoian S, Pirola CJ. Genetic predisposition in nonalcoholic fatty liver disease. Clin Mol Hepatology 2017; 23(1): 1-12.
15. Jensen MD, Ryan DN, Apovian CM et al. 2013 АНА/АСС/Т0S Guideline for the Management of Overweight and Obesity in Adults: A report of the American College of Cardiology American Heart Association Task force on Practice Guidelines and The Obesity Society. Circulation 2014; 129(Suppl 2): 102-138.
16. Sheremet MI, Sydorchuk LP, Shidlovskyi VO, Bedenyuk AD. Research of prognostic markers of proliferation and apoptosis in patients with nodular goiters combined with autoimmune thyroiditis. Arch Balkan Med Union 2016; 51(4): 488-491.
17. Zhou YJ, Li YY, Nie YQ et al. Influence of polygenetic polymorphisms on the susceptibility to non-alcoholic fatty liver disease of Chinese people. J Gastroenterol Hepatol 2010; 25(4): 772-777.
18. Becer EC. Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 gene on lipid profile and adipokines levels in obese subjects. A Balkan J Med Genet 2017; 20(1): 71-80.
19. Motavallian A, Andalib S, Vaseghi G et al. Association between Pro12Ala polymorphism of the PPAR-γ2 gene and type 2 diabetes mellitus in Iranian patients. Indian J Hum Genet 2013; 19(2): 239-244.
20. Tekatas DD, Bahcecioglu IH, Ispiroglu M, et al. Role of renin-angiotensin-converting enzyme level and ACE gene polymorphism in patients with nonalcoholic fatty liver disease. Euroasian J Hepato-gastroenterol 2016; 6(2): 137-142.
Once an article is accepted for publication, MSJ requests a transfer of copyrights for published articles.
COPYRIGHT TRANSFER FORM FOR
REVISTA MEDICO-CHIRURGICALĂ A SOCIETĂȚII DE MEDICI ȘI NATURALIȘTI DIN IAȘI /
THE MEDICAL-SURGICAL JOURNAL OF THE SOCIETY OF PHYSICIANS AND NATURALISTS FROM IASI
We, the undersigned authors of the manuscript entitled
warrant that this manuscript, which is submitted for publication in the REVISTA MEDICO-CHIRURGICALĂ, has not been published and it is not under consideration for publication in another journal.
- we give the consent for publication in the REVISTA MEDICO-CHIRURGICALĂ, in printed and electronic format and we transfer unconditioned and complete the copyright of this manuscript to the REVISTA MEDICO-CHIRURGICALĂ, in the event of its acceptance.
- the manuscript does not break the intellectual property rights of any other person.
- we have read the submitted version of the manuscript and we are fully responsible for the content.
Names and signatures of authors / copyright owners (the following sequence is the authorship of the article):
N.B. All the authors must sign this form