Association between PPARGC1A single nucleotide polymorphisms and increased risk of nonalcoholic fatty liver disease among Iranian patients with type 2 diabetes mellitus

Association between PPARGC1A single nucleotide polymorphisms and increased risk of nonalcoholic fatty liver disease among Iranian patients with type 2 diabetes mellitus

Background/aim: Environmental and genetic factors may play a major role in the development of nonalcoholic fatty liver disease(NAFLD) among people with obesity and type 2 diabetes mellitus. Based on the fact that PGC-1α, as the protein encoded by thePPARGC1A gene, plays a key role in energy metabolism pathways, it has been hypothesized that polymorphisms within the PPARGC1Agene may be associated with increased risks of NAFLD. Thus, this study was designed to evaluate the Gly482Ser polymorphism(rs8192678) within the PPARGC1A gene and its association with the increased risk of NAFLD in Iranian patients with type 2 diabetes.Materials and methods: A total of 145 NAFLD patients with a history of type 2 diabetes and 145 healthy control subjects were includedin the study. Gly482Ser polymorphism genotyping was done using the amplification refractory mutation system-polymerase chainreaction (ARMS-PCR) technique.Results: The results showed a significant difference between the PPARGC1A Gly482Ser polymorphism in NAFLD patients and thehealthy controls. Accordingly, the AA genotype and A allele were increased in the NAFLD patients when compared to the healthycontrols. However, no significant correlation was observed between the Gly482Ser polymorphism and the physiological and biochemicalparameters.Conclusion: Based on the results, the AA genotype, which is associated with the insertion of Ser, can be considered as a risk factor forthe development of NAFLD in Iranian patients with diabetes type 2.

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  • 1. Milic S, Mikolasevic I, Krznaric-Zrnic I, Stanic M, Poropat G et al. Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options. Drug Design, Development and Therapy 2015; 9: 4835-4845. doi: 10.2147/DDDT.S64877
  • 2. Moley KH, Colditz GA. Effects of obesity on hormonally driven cancer in women. Science Translational Medicine 2016; 8 (323): 323ps3. doi: 10.1126/scitranslmed.aad8842
  • 3. Targher G, Bertolini L, Padovani R, Rodella S, Zoppini G et al. Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease. Diabetes Care 2006; 29 (6): 1325-1330. doi: 10.2337/dc06-0135
  • 4. Saremi L, Lotfipanah S, Mohammadi M, Hosseinzadeh H, Sayad A et al. Association of HFE gene mutations with nonalcoholic fatty liver disease in the Iranian population. Cellular and Molecular Biology (Noisy-le-Grand) 2016; 62 (12): 123-128. doi: 10.14715/cmb/2016.62.12.2
  • 5. Saremi L, Lotfipanah S, Mohammadi M, Hosseinzadeh H, Fathi-Kazerooni M et al. The Pro12Ala polymorphism in the PPAR-γ2 gene is not associated with an increased risk of NAFLD in Iranian patients with type 2 diabetes mellitus. 2019; 24: 12. doi: 10.1186/s11658-019-0138-0
  • 6. Dongiovanni P, Rametta R, Fracanzani AL, Benedan L, Borroni V et al. Lack of association between peroxisome proliferatoractivated receptors alpha and gamma2 polymorphisms and progressive liver damage in patients with non-alcoholic fatty liver disease: a case control study. BMC Gastroenterology 2010; 10 (102): 102. doi: 10.1186/1471-230X-10-102
  • 7. Portillo-Sanchez P, Cusi K. Treatment of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus. Clinical Diabetes and Endocrinology 2016; 2 (9): 9. doi: 10.1186/s40842-016-0027-7
  • 8. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002; 123 (1): 134-140. doi: 10.1053/ gast.2002.34168
  • 9. Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129 (1): 113-121. doi: 10.1053/j.gastro.2005.04.014
  • 10. Yoneda M, Hotta K, Nozaki Y, Endo H, Uchiyama T et al. Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD). BMC Gastroenterolgy 2008; 8 (27): 27. doi: 10.1186/1471-230X-8-27
  • 11. Burgueno AL, Cabrerizo R, Gonzales Mansilla N, Sookoian S, Pirola CJ. Maternal high-fat intake during pregnancy programs metabolic-syndrome-related phenotypes through liver mitochondrial DNA copy number and transcriptional activity of liver PPARGC1A. Journal of Nutritional Biochemistry 2013; 24 (1): 6-13. doi: 10.1016/j.jnutbio.2011.12.008
  • 12. Saremi L, Saremi M, Lotfipanah S, Imani S, Zhang T et al. Relation between PPARGC1A gene polymorphisms with the increased risk of coronary artery disease among patients with type 2 diabetes mellitus in Iran. General Endocrinology 2015; 11 (1): 13-17. doi: 10.4183/aeb.2015.13
  • 13. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry 1972; 18 (6): 499-502.
  • 14. Pappachan JM, Babu S, Krishnan B, Ravindran NC. Nonalcoholic fatty liver disease: a clinical update. Journal of Clinical and Translational Hepatology 2017; 5 (4): 384-393. doi: 10.14218/JCTH.2017.00013
  • 15. Liang H, Ward WF. PGC-1α: a key regulator of energy metabolism. Advances in Physiology Education 2006; 30 (4): 145-151. doi: 10.1152/advan.00052.2006
  • 16. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. New England Journal of Medicine 2004; 350: 664-671. doi: 10.1056/NEJMoa031314
  • 17. Hara K, Tobe K, Okada T, Kadowaki H, Akanuma Y et al. A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to type II diabetes. Diabetologia 2002; 45 (5): 740-743. doi: 10.1007/s00125-002-0803-z
  • 18. Muller YL, Bogardus C, Pedersen O, Baier L. A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians. Diabetes 2003; 52 (3): 895-898. doi: 10.2337/diabetes.52.3.895
  • 19. Iff J, Wang W, Sajic T, Oudry N, Gueneau E et al. Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis. Journal of Proteome Research 2009; 8 (10): 4511-4524. doi: 10.1021/ pr9003272.
  • 20. Hui Y, Yu-Yuan L, Yu-Qiang N, Wei-Hong S, Yan-Lei D et al. Effect of peroxisome proliferator-activated receptors-gamma and co-activator-1α genetic polymorphisms on plasma adiponectin levels and susceptibility of non-alcoholic fatty liver disease in Chinese people. Liver International 2008; 28 (3): 385-392. doi: 10.1111/j.1478-3231.2007.01623.x
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: 6
  • Yayıncı: TÜBİTAK
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