THE ROLE OF GENETIC VARIATION SINGLE NUCLEOTIDE POLYMORPHISM T45G AND SINGLE NUCLEOTIDE POLYMORPHISM G276T OF THE ADIPONECTIN GENE IN FATTY LIVER PATHOMECHANISM ON OBESE MALE SUBJECT
DOI:
https://doi.org/10.22159/ajpcr.2018.v11s1.26615Keywords:
Genetic variation, Adiponectin, Fatty liverAbstract
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 Objective: The aim of this study was to observe the role of genetic variation T45G and G276T of adiponectin gene in pathomechanism of fatty liver on obese subjects.
Methods: An observational study with case–control design was conducted on 94 obese male subjects (50 subjects are obese male with fatty liver and 44 subjects are obese male without fatty liver). The research is taken place in Prodia Clinical Laboratory Makassar to determine genetic variation single nucleotide polymorphism (SNP) T45G (Genotype TT, thyroglobulin [TG], and GG) and SNP G276T (Genotype GG, GT, and TT) of adiponectin gene, technique of polymerase chain reaction-restriction fragment length polymorphism was used. The level of adiponectin, soluble tumor necrosis factor-α receptor 2 (sTNF-αR2), and insulin serum were measured by enzyme-linked immunosorbent assay method, meanwhile, fatty liver was detected by ultrasonography.
Results: The result of the study showed genetic variation, T45G of adiponectin gene was genotype TT 62.8 %, genotype TG 30.9%, and genotype GG 6.3%; meanwhile, genetic variation G276T of adiponectin gene was genotype GG 43.6%, genotype GT 38.3 %, and genotype TT 18.1 %. There was no significant correlation of genetic variation T45G as well as G276T of adiponectin gene, to the level of adiponectin serum (>0.05). Insulin resistance was more frequent on genotype TT genetic variation T45G of adiponectin gene as compare to that on TG+GG (p=0.069). Genotype TT on genetic variation T45G of adiponectin gene was significant correlated with fatty liver (p=0.010). Genotype TG+TT on genetic variation G276T of adiponectin gene was more likely to have insulin resistance and fatty liver than that of genotype GG. Allele T carrier on genetic variation T45G and G276T of adiponectin gene had a higher chance to have insulin resistance and fatty liver as compare to that of allele G carrier. The odds ratio of having fatty liver insulin resistance is 5.3, genotype TT on genetic variation T45G of adiponectin gene is 3.8, low level of adiponectin is 3.4, and high level of sTNF-αR2 is 3.3.
Conclusion: Genotype TT on genetic variation T45G of adiponectin gene has a role in fatty liver on obese subjects. Genotype TG+TT on genetic variation G276T of adiponectin gene was more high frequent to have fatty liver compare to that on genotype GG. Allele T carrier on genetic variation T45G of adiponectin gene had higher frequency on the occurrence of insulin resistance than that on allele G carrier. Insulin resistance has the highest influence as compare to genotype TT on genetic variation T45G of adiponectin gene, low level of adiponectin serum, high level of sTNF-αR2 serum in the pathomechanism of fatty liver in obese subjects.
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References
Sanyal AJ. Mechanisms of disease: Pathogenesis of nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 2005;2:46-53.
Arun JS. In: Farrell GC, George J, Hall PM, McCullough AJ. The Pathogenesis of NASH: Human Studies, Fatty Liver Disease NASH and Related Disorders. Oxford: Blackwell Publishing Ltd.; 2005. p. 76- 90.
Ahmed H, Salem A, Mohamed M, Shahat A, Khalil W, Mohamed, S. Experimental evidences for the promising therapeutic role of vitis vinifera seed extract against nonalcoholic steatohepatitis. Int J of Pharm and Pharmaceutical Sci 2014;7(2):417-424.
Kim C, 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 Gastroentrol 2005;11:5314-21.
Dyck DJ, Heigenhauser GJ, Bruce CR. The role of adipokines as regulators of skeletal muscle fatty acid metabolism and insulin sensitivity. Acta Physiol (Oxf) 2006;186:5-16.
Saad E, Habib S, Refai W, Elfayoumy A. Malondialdehyde adiponectin, nitric oxide, c-reactive protein, tumor necrosis-alpha and insulin resistance relationships and inter-realtiponships in type 2 diabetes early stage is metformmin alone adequate in this stage. Int J of Pharm and Pharmaceutical Sci 2017;9(10):176-181.
Bloedl UC, Lehrke M, Fleischer-Brielmaier E, Tietz AB, Nagel JM, Göke B, et al. Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL level in patients with metabolic syndrome. Cardiovasc Diabetol 2006;5:1-7.
Wiecek A, Adamczak M, Chudek J. Adiponectin–An adipokine with unique metabolic properties. Nephrol Dial Transplant 2007;22:981-8.
Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005;96:939-49.
Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J, et al. Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 2004;40:46-54.
González-Sánchez JL, Zabena CA, MartÃnez-Larrad MT, Fernández- Pérez C, Pérez-Barba M, Laakso M, et al. An SNP in the adiponectin gene is associated with decreased serum adiponectin levels and risk for impaired glucose tolerance. Obes Res 2005;13:807-12.
Xita N, Georgiou I, Chatzikyriakidou A, Vounatsou M, PapassotiriouGP, Papassotiriou I, et al. Effect of adiponectin gene polymorphisms on circulating adiponectin and insulin resistance indexes in women with polycystic ovary syndrome. Clin Chem 2005;51:416-23.
Zacharova J, Chiasson JL, Laakso M, STOP-NIDDM Study Group. The common polymorphisms (single nucleotide polymorphism [SNP] +45 and SNP +276) of the adiponectin gene predict the conversion from impaired glucose tolerance to Type 2 diabetes: The STOP-NIDDM trial. Diabetes 2005;54:893-9.
Lawrence G, et al. The Interaction of Free Fatty Acid, Total Antioxidant Status, Palsminogen Activator Inhibitor-1, Adiponectin and high sensitivity C-Reactive Protein on The Occurence of Impaired Glucose Tolerance, Disertasi, Universitas Hasanuddin Makassar; 2005.
Mackevics V, Heid IM, Wagner SA, Cip P, Doppelmayr H, Lejnieks A, et al. The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy caucasians. Eur J Hum Genet 2006;14:349-56.
Wang Y, Zhou M, Lam KS, Xu A. Protective roles of adiponectin in obesity-related fatty liver diseases: Mechanisms and therapeutic implications. Arq Bras Endocrinol Metabol 2009;53:201-12.
Hsieh CJ, Wang PW, Hu TH. Association of adiponectin gene polymorphism with nonalcoholic fatty liver disease in taiwanese patients with type 2 diabetes. Liu C-J, Ed. Plos one 2015;10(6):e0127521.
Musso G, Gambino R, De Michieli F, Durazzo M, Pagano G, Cassader M, et al. Adiponectin gene polymorphisms modulate acute adiponectin response to dietary fat: Possible pathogenetic role in NASH. Hepatology 2008;47:1167-77.
Yoon D. Hypoadiponectinemia and insulin resistance are associated with nonalcoholic fatty liver disease. J Korean Med Sci 2005;20:421-6.
Kowalska I, Straczkowski M, Nikołajuk A, Krukowska A, Kinalska I, Górska M, et al. Plasma adiponectin concentration and tumor necrosis factor-alpha system activity in lean non-diabetic offspring of Type 2 diabetic subjects. Eur J Endocrinol 2006;154:319-24.
Dzienis-Straczkowska S, Straczkowski M, Szelachowska M, Stepien A, Kowalska I, Kinalska I, et al. Soluble tumor necrosis factor-alpha receptors in young obese subjects with normal and impaired glucose tolerance. Diabetes Care 2003;26:875-80.
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