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Abstract
Introduction. Nowadays nonalcoholic fatty liver disease (NAFLD) consider as multisystem disease that is primarily associated with components of the metabolic syndrome and is associated with cardiovascular and renal impairment. The comorbidity of NAFLD with renoparenchymal arterial hypertension (RPAH) has not been sufficiently studied.
The purpose of the study was to investigate the influence of G276T genetic polymorphism of ADIPOQ on the severity of metabolic disorders, inflammation, liver, artery and kidney damage in the comorbidity of NAFLD and RPAH.
Materials and methods. The study included 87 patients with comorbidity of NAFLD and RPAH, grade 2. The mean age of patients was 50.78 ± 9.35 years. The vast majority of patients were overweight or obese. The control group was composed of 20 healthy volunteers. Parameters of carbohydrate and lipid metabolism, liver and kidney’s function, adiponectin, fetuin-A, cytokeratin-18, pro-inflammatory cytokines levels were investigated. For diagnostic of non-alcoholic steatosis and indication parameters of arteries, an ultrasound method was used.
Results. It was found that the T allele was detected in 62 (35.6%) patients of the main group, which was significantly (p<0,05) different from the control group (22.5%). In the presence of patients with comorbidity NAFLD and RPAH G/T and T/T genotypes, carbohydrate metabolism disorders are more pronounced than in the G/G genotype. Thus, index HOMA in this group was 4.52 ± 0.87, which was significantly higher than patients with G/G genotype - 3.77 ± 0.53 (p <0.01).The G276T polymorphism of the ADIPOQ is not associated with markers of liver and kidney damage in patients with NAFLD + RPAH. The presence of G/T and T/T genotypes in patients with comorbidity of NAFLD and RPAH is associated with an increase in interleukin-6 and fetuin-A compared to the G/G genotype. Patients with comorbidity of NAFLD + RPAH and with the T allele of the polymorphic marker G276T of the ADIPOQ gene are more likely to have impaired endothelium-dependent vasodilation, indicating more significant vascular reactivity disorders - 7.72 ± 1.25% for the genotype G/G, and 7.00 ± 1.10% for the genotype G/T (p <0,01).
Conclusions. The presence of the T allele of the polymorphic marker G276T of the ADIPOQ is associated with the development of comorbidity of NAFLD and RPAH.
References
Adams LA, Anstee QM, Tilg H, Targher G. (2017) Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut. 2017;66(6): 1138-53. doi: 10.1136/gutjnl-2017-313884
Byrne CD, Targher G. (2015) NAFLD: a multisystem disease. J. Hepatol. 2015;62 (1 Suppl):S47-64. doi: 10.1016/j.jhep.2014.12.012
Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J. (2004) Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology. 2004;40:46–54.
Iminova DA, Alyavi AL, Sobirova GN (2019) Association of Gene Polymorphism Adipoq +276 (G / T) with Surrogatic Markers of the Increased Fat Content in the Liver. American Journal of Medicine and Medical Sciences. 2019; 9(12): 464-466. DOI: 10.5923/j.ajmms.20190912.03
Ix JH, Sharma K. (2010) Mechanism linking obesity, chronic kidney disease and fatty liver disease: the roles of fetuin-A, adiponectin and AMPK. J Am Soc Nephrol. 2010;21(3):406-12.
Kanda T, Matsuoka S, Yamazaki M. (2018) Apoptosis and non-alcoholic fatty liver diseases. World J Gastroenterol. 2018;24(25): 2661-72. doi: 10.3748/wjg.v24.i25.2661
Kawaguchi T, Sumida Y, Umemura A, Matsuo K, Takahashi M, Takamura T, et al.; Japan Study Group of Nonalcoholic Fatty Liver Disease. (2012) Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese. PLoS One. 2012;7(6):e38322. doi: 10.1371/journal.pone.0038322
Lin CH, Ho CY, Liu CS. (2012) Influence of Adiponectin Gene Polymorphisms on Adiponectin Serum Level and Insulin Resistance Index in Taiwanese Metabolic Syndrome Patients. Chin J Physiol. 2012;55(6):405-411.
Liu J, Xing J, Wang B, Wei C, Yang R, Zhu Y, Qiu H (2019) Correlation Between Adiponectin Gene rs1501299 Polymorphism and Nonalcoholic Fatty Liver Disease Susceptibility: A Systematic Review and Meta-Analysis. Med Sci Monit. 2019; 25: 1078–1086. doi: 10.12659/MSM.912737.
Lowry DE, Fenwick PH, Roke K, Jeejeebhoy K, Dhaliwal R, Brauer P, et al. (2018) Variants in APOA5 and ADIPOQ Moderate Improvements in Metabolic Syndrome during a One-Year Lifestyle Intervention. Lifestyle Genom. 2018;11(2):80-9. doi: 10.1159/000494331
Mantovani A, Zusi C, Sani E, Colecchia A, Lippi G, Zaza GL, et al. (2019) Association between PNPLA3rs738409 polymorphism decreased kidney function in postmenopausal type 2 diabetic women with or without non-alcoholic fatty liver disease. Diabetes Metab. 2019;45:480-7.
Mohseni F, Moghbelinejad S, Najafipour R (2017) Major Components of Metabolic Parameters and Nutritional Intakes in Different Genotypes of Adiponectin +276 G>T Gene Polymorphism in Non-Diabetes and Non-Alcoholic Iranian Fatty Liver Patients. Avicenna J Med Biotechnol. 2017; 9(3): 155–161. PMCID: PMC5501145
Semple RK (2017) How does insulin resistance arise, and how does it cause disease? Human genetic lessons. European Journal of Endocrinology. 2017; 174: R209–R223.
Shalimova A, Fadieienko G, Kolesnikova O, Isayeva A, Zlatkina V, Nemtsova V, Prosolenko K, Psarova V, Kyrychenko N, Kochuieva M (2019) The role of genetic polymorphism in the formation of arterial hypertension, type 2 diabetes and their comorbidity, Current Pharmaceutical Design. 2019, 25, 218-227.
Sheng T, Yang K. (2008) Adiponectin and its association with insulin resistance and type 2 diabetes. J Genet Genom. 2008;35:321-326.
Siitonen N, Pulkkinen L, Lindström J. (2011) Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the Finnish Diabetes Prevention Study. BMC Med Genet. 2011;10:12-15.
Targher G, Bertolini L, Rodella S, Lippi G, Zoppini G, Chonchol M. (2010) Relationship between kidney function and liver histology in subjects with nonalcoholic steatohepatitis. Clin J Am Soc Nephrol. 2010;5(12):2166-71. doi: 10.2215/CJN.05050610
Thrasher T, Abdelmalek MF. (2016) Nonalcoholic fatty liver disease. N C Med J. 2016;77 (3):216-9.
Wang BF, Wang Y, Ao R, Tong J, Wang BY (2016) AdipoQ T45 G and G276 T Polymorphisms and Susceptibility to Nonalcoholic Fatty Liver Disease Among Asian Populations: A Meta-Analysis and Meta-Regression. J Clin Lab Anal. 2016; 30(1): 47-57. doi: 10.1002/jcla.21814.
Whitehead JP, Richards AA, Hickman IJ. (2006) Adiponectin — a key adipokine in the metabolic syndrome. Diab, Obes, Metabol. 2006;8:264-280.
Xu Y, Xu M, Bi Y, et al. (2011) Serum fetuin-A is corretaled with metabolic syndrome in middle-aged and elderly Chinese. Atherosclerosis 2011;216(1):180-6.
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