Clinical and genetic characteristics of patients with obesity and non-alcoholic fatty liver disease

Authors

DOI:

https://doi.org/10.22141/2308-2097.54.4.2020.216713

Keywords:

ultrasound steatometry, controlled attenuation parameter, rs1801282 (Pro12Ala) polymorphism of PPAR-γ2 gene

Abstract

Backgrounds. Currently, the rs1801282 (Pro12Ala) polymorphism in PPAR-γ2 (peroxisome proliferator-activated receptor gamma) gene is important for the pathogenesis of both obesity and non-alcoholic fatty liver disease (NAFLD). However, the clinical and laboratory characteristics in Ukrainian patients with combined pathology have not yet been studied based on this polymorphism. The purpose was to study the clinical and laboratory features of patients with obesity and NAFLD depending on rs1801282 polymorphism in PPAR-γ2 gene. Materials and methods. The study involved 123 patients with obesity 1–3 classes and NAFLD. All patients underwent a molecular genetic study of rs1801282 polymorphism in PPAR-γ2 gene, as well as anthropometric measurements, laboratory and instrumental examinations (including ultrasound (US) steatometry). Results. The study revealed in patients with CG and GG genotypes rs1801282 polymorphism of PPAR-γ2 gene significantly much higher levels of body mass index (p = 0.03), fasting glucose (p = 0.02), insulin (p < 0.0001), and C-peptide (p = 0.02), ALT (p = 0.04), GGTP (p < 0.0001), total cholesterol (p = 0.03), triglycerides (p = 0.002), low-density lipoprotein cholesterol (p = 0.004), very low-density lipoprotein cholesterol (p = 0.001), atherogenic factor (p < 0.0001), except for levels of CAP (p = 0.002), stimulated insulin (p < 0.0001), serum uric acid (p = 0.008), and high-density lipoprotein cholesterol (p < 0.0001) that were significantly less higher compared to CC genotype. Conclusions. In Ukrainians with a combined course of obesity and NAFLD, the carriers of the G allele rs1801282 polymorphism of PPAR-γ2 gene have been shown to have significant metabolic differences that might be associated with protection against the development of steatosis and type 2 diabetes, however increase cardiovascular risk.

References

Alfredo JM, Milagro FI. Genetics of weight loss: A basis for personalized obesity management. Trends Food Sci Technol. 2015;42(2):97-115. doi:10.1016/j.tifs.2014.12.007.

Alonso R, Farías M, Alvarez V, Cuevas A. The Genetics of Obesity. In: Rodriguez-Oquendo A, editor. The Genetics of Obesity. Translational Cardiometabolic Genomic Medicine. London: Elsevier Science Publishing Co Inc; 2016. 161-177 pp.

Goodarzi MO. Genetics of obesity: what genetic association studies have taught us about the biology of obesity and its complications. Lancet Diabetes Endocrinol. 2018 Mar;6(3):223-236. doi:10.1016/S2213-8587(17)30200-0.

Singh RK, Kumar P, Mahalingam K. Molecular genetics of human obesity: A comprehensive review. C R Biol. 2017 Feb;340(2):87-108. doi:10.1016/j.crvi.2016.11.007.

Walter S, Mejía-Guevara I, Estrada K, Liu SY, Glymour MM. Association of a Genetic Risk Score With Body Mass Index Across Different Birth Cohorts. JAMA. 2016 Jul 5;316(1):63-9. doi:10.1001/jama.2016.8729.

Mao L, Fang Y, Campbell M, Southerland WM. Population differentiation in allele frequencies of obesity-associated SNPs. BMC Genomics. 2017 Nov 10;18(1):861. doi:10.1186/s12864-017-4262-9.

Sookoian S, Pirola CJ. Genetic predisposition in nonalcoholic fatty liver disease. Clin Mol Hepatol. 2017 Mar;23(1):1-12. doi:10.3350/cmh.2016.0109.

Dongiovanni P, Romeo S, Valenti L. Genetic Factors in the Pathogenesis of Nonalcoholic Fatty Liver and Steatohepatitis. Biomed Res Int. 2015;2015:460190. doi:10.1155/2015/460190.

Schwimmer JB, Celedon MA, Lavine JE, et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology. 2009 May;136(5):1585-92. doi:10.1053/j.gastro.2009.01.050.

Loomba R, Schork N, Chen CH, et al; Genetics of NAFLD in Twins Consortium. Heritability of Hepatic Fibrosis and Steatosis Based on a Prospective Twin Study. Gastroenterology. 2015 Dec;149(7):1784-93. doi:10.1053/j.gastro.2015.08.011.

Ramos-Lopez O, Milagro FI, Allayee H, et al. Guide for Current Nutrigenetic, Nutrigenomic, and Nutriepigenetic Approaches for Precision Nutrition Involving the Prevention and Management of Chronic Diseases Associated with Obesity. J Nutrigenet Nutrigenomics. 2017;10(1-2):43-62. doi:10.1159/000477729.

Kovalic AJ, Banerjee P, Tran QT, Singal AK, Satapathy SK. Genetic and Epigenetic Culprits in the Pathogenesis of Nonalcoholic Fatty Liver Disease. J Clin Exp Hepatol. 2018 Dec;8(4):390-402. doi:10.1016/j.jceh.2018.04.001.

Wolf Greenstein A, Majumdar N, Yang P, Subbaiah PV, Kineman RD, Cordoba-Chacon J. Hepatocyte-specific, PPARγ-regulated mechanisms to promote steatosis in adult mice. J Endocrinol. 2017 Jan;232(1):107-121. doi:10.1530/JOE-16-0447.

Takahashi K, Nakamura H, Sato H, Matsuda H, Takada K, Tsuji T. Four Plasma Glucose and Insulin Responses to a 75 g OGTT in Healthy Young Japanese Women. J Diabetes Res. 2018 Jan 30;2018:5742497. doi:10.1155/2018/5742497.

Maciejewska-Skrendo A, Pawlik A, Sawczuk M, et al. PPARA, PPARD and PPARG gene polymorphisms in patients with unstable angina. Gene. 2019 Aug 30;711:143947. doi:10.1016/j.gene.2019.143947.

Lee YK, Park JE, Lee M, Hardwick JP. Hepatic lipid homeostasis by peroxisome proliferator-activated receptor gamma 2. Liver Res. 2018 Dec;2(4):209-215. doi:10.1016/j.livres.2018.12.001.

Wang Y, Nakajima T, Gonzalez FJ, Tanaka N. PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice. Int J Mol Sci. 2020 Mar 17;21(6):2061. doi:10.3390/ijms21062061.

Barros RK, Cotrim HP, Daltro CH, Oliveira YA. Hyperferritinemia in patients with nonalcoholic fatty liver disease. Rev Assoc Med Bras (1992). 2017 Mar;63(3):284-289. doi:10.1590/1806-9282.63.03.284.

Gorovenko NG, Prysyazhnyuk VP, Rossokha ZI. Association of Pro12Ala polymorphism of PPAR-γ gene with blood biochemical parameters, cytokine and adypokine profiles, structural and functional parameters of liver in patients with nonalcoholic fatty liver disease. Ukrainian Medical Journal. 2017;5(121):144-147. (in Ukrainian).

Published

2020-09-01

Issue

Section

Original Researches