Combined influence of polymorphic variants of PPAR-2 (rs1801282) and ACE (rs4646994) genes on the onset of non-alcoholic fatty liver disease in patients with essential arterial hypertension and obesity

Yu. M. Yarynych, L. P. Sydorchuk

Abstract


Objective: to study a combined influence of polymorphic variants of PPAR-g2 (rs1801282) and ACE (rs4646994) genes on the onset of non-alcoholic fatty liver disease (NAFLD) in patients with essential arterial hypertension (EAH) and obesity.

Materials and methods: The study involved 96 patients with NAFLD, stage II EAH of the 1-2 degrees, with high and very high risk with associated AO including males - 41.67% (40), women - 58.33% (56), the average age was 53.70 ± 5.34 years. The function of the liver was studied by the activity of organ-specific enzymes. The polymorphism of PPAR-g2 (Pro12Ala) and ACE (I / D) genes was studied  by the PCR method. The control group consisted of 50 virtually healthy individuals.

Results. A third of patients with NAFLD (31.25%) are carriers of an unfavorable combination of homozygous deletion of the ACE gene (rs4646994) and the ProPro genotype of the PPAR-g2 gene (rs1801282) (DD / Pro12), and one in five (22.92%) is a carrier of a heterozygote combination for two genes (ID / ProAla variant), which is by 2.6 and 2.9 times more frequent than in the control group (p = 0.01 and p = 0.025, respectively). The controls are dominated by individuals with a combination of the ID-polymorphic variant of the ACE gene and the ProPro genotype of the PPAR-γ2 gene by 1.84 times: 44.0% versus 23.96% (c2=6,19, р=0,013). The risk of NAFLD in the surveyed population of the inhabitants of Northern Bukovyna increases with a combination of the Ala allele of the PPAR-g2 gene and the ID-genotype of the gene ACE (ID / ProAla, ID / 12Ala variants) by 2.3 times (OR = 3.17, 95% CI OR = 1.13-8.88, p = 0.023), due to NASH – by 4.4 times (OR = 7.0, 95% CI OR = 1.81-27.07, p = 0.006). While the dominant effect of the homozygous deletion of the ACE gene, without the significant effect of the Pro12-genotype of the PPAR-γ2 gene, on the owners of the DD / Pro12 variant, increases the risk of NAFLD by 2.6 times (OR = 3.33, 95% CI OR = 1.28 -8.68, p = 0.01), due to NALS – by 2.7 times (OR = 3.53, 95% CI OR = 1.33-9.34, p = 0.008), respectively. Instead, the combination of the I-allele of the ACE gene and the Pro-allele of the PPAR-γ2 gene is protective with the lowest chance of NAFLD (OR = 0.40, 95% CI OR = 0.19-0.83, p = 0.013) and its subtypes, especially steatohepatitis (OR = 0.08, 95% CI OR = 0.01-0.69, p = 0.006) than liver steatosis (OR = 0.48, 95% CI OR = 0.23-1, 01, p = 0,051).

Conclusions: Having the DD genotype of the ACE gene in combination with the Pro12 genotype of the PPAR-γ2 gene increases the risk of NAFLD by 2.6 times (due to non-alcoholic liver steatosis). The combination of the I-allele of the ACE gene and the Pro-allele of the PPAR-γ2 gene is protective with the lowest chance of NAFLD in the population (especially of non-alcoholic steatohepatitis).


Keywords


non-alcoholic fatty liver disease, PPAR-2 і АСЕ genes, arterial hypertension, obesity

Full Text:

PDF

References


Bellentani S, Scaglioli F, Marino M, Bedogni G. Epidemiology of non-alcoholic fatty liver disease // Dig Dis. 2010; 28: 155-61.

Takuma Y, Nouso K. Nonalcoholic steatohepatitis-associated hepatocellular carcinoma: Our case series and literature review. World J. Gastroenterol. 2010; 16(12): 1436-41.

L.P. Sydorchuk, A.A. Sokolenko, A.R. Sydorchuk [et al.]//. Insulin resistance in patients with arterial hypertension and abdominal obesity depending on ACE and PPAR-γ2 genes polymorphism: a new opinion concerning an old problem/ The New Armenian Medical Journal. – 2015. - Vol. 9, № 2. - Р. 43-51.

Niu W, Qi Y. Circulating cholesteryl ester transfer protein and coronary heart disease: mendelian randomization meta-analysis. Circ Cardiovasc Genet. 2015; 8(1): 114-21. doi: 10.1161/CIRCGENETICS.114.000748.

Settin A, El-Baz R, Ismaeel A, Tolba W, Allah WA. Association of ACE and MTHFR genetic polymorphisms with type 2 diabetes mellitus: Susceptibility and complications. Journal of the Renin-Angiotensin Aldosterone System 2015; 16(4): 838-43. DOI: 10.1177/1470320313516172 jra.sagepub.com

Sydorchuk LP, Gaborec IY, Sydorchuk AR, Ursulyak YuV, Sokolenko AA, Ivashchuk SI 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.

Kramer H, Gutiérrez OM, Judd SE, Muntner P, Warnock DG, Tanner RM. et al. Waist Circumference, Body Mass Index, and ESRD in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study. Am J Kidney Dis. 2016; 67(1): 62-9. doi: 10.1053/j.ajkd.2015.05.023.

Lapice E, Vaccaro O. Interaction between Pro12Ala polymorphism of PPARγ2 and diet on adiposity phenotypes. Curr Atheroscler Rep. 2014; 16(12): 462. doi: 10.1007/s11883-014-0462-9.

Sydorchuk L, Sokolenko A, Sydorchuk A, Korovenkova O, Sydorchuk R, Sokolenko M. Insulin resistance changes in obese hypertensive patients under the influence of treatment depending on ACE (I/D), PPAR-g2 (Pro12Ala) genes polymorphism. The Pharma Innovation J. 2015; 3(12): 57–63.

Order of the Ministry of Health of Ukraine of November 6, 2014, No. 826 "On approval and implementation of medical and technological documents for the standardization of medical care in patients with chronic non-infectious hepatitis". "Unified clinical protocol of primary, secondary (specialized) medical aid: non-alcoholic steatohepatitis", "Non-alcoholic fatty liver disease. Adapted clinical approach, based on evidence." K .: Ministry of Health, 2014. 29/55 [1] p.

Instructions and a clinical protocol for the provision of medical aid "Arterial hypertension". Order of the Ministry of Health of Ukraine of May 24, 2012 No. 384 "On approval and implementation of medical and technological documents for the standardization of medical care in arterial hypertension" / Working group on arterial hypertension of the Ukrainian Association of Cardiologists. K .: Ministry of Health, 2012. 108 [1] p.

Jensen MD, Ryan DN, Apovian CM, Ard JD, Comuzzie AG, Donato KA, 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, 2013.Online Version: http://circ.ahajournals.org/contenent/early/2013/11/11/01.cir.0000437739.71477.ee.citation

Entrez Gene. Sequence analysis 2017. National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov. 2017.




DOI: http://dx.doi.org/10.5281/zenodo.1207053

Refbacks

  • There are currently no refbacks.




Copyright (c) 2018 © The Author (s) 2018

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Journal of Education, Health and Sport formerly Journal of Health Sciences

Declaration on the original version.

Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

Archives 2011 - 2014

PBN 2011 - 2014

https://pbn.nauka.gov.pl/sedno-webapp/search?search&searchCategory=WORK&filter.inJournal=36616

POL-index 2011 - 2014

https://pbn.nauka.gov.pl/polindex-webapp/browse/journal/journal-32a319c5-a850-4f44-ba70-1418a6087655

BASE 2011 - 2014

https://www.base-search.net/Search/Results?lookfor=Journal+of+Health+Sciences+%28Radom%29&type=all&oaboost=1&ling=1&name=&thes=&refid=dcrespl&newsearch=1

http://elibrary.ru/contents.asp?titleid=37467

http://journal.rsw.edu.pl/index.php/JHS/issue/archive

Indexed in Bases, Bazy indeksacyjne: ERIH Plus, Worldcat, PBN/POL-Index, ICI Journals Master List, Directory of Open Access Journals (DOAJ), ZBD, Ulrich's periodicals, Google Scholar, Polska Bibliografia Lekarska

US NLM = 101679844

101679844 - NLM Catalog Result - NCBI

https://www.ncbi.nlm.nih.gov/nlmcatalog/101679844

Find a library that holds this journal: http://worldcat.org/issn/23918306

Journal Language(s): English 

PBN Poland

https://pbn.nauka.gov.pl/sedno-webapp/journals/49068

POL-index

https://pbn.nauka.gov.pl/polindex-webapp/browse/journal/journal-c39c8169-88d2-45db-9e7f-d948ce9981c4

BASE

https://www.base-search.net/Search/Results?join=AND&bool0[]=AND&lookfor0[]=2391-8306&type0[]=all&page=11&l=pl&oaboost=1&refid=dcpagepl

Redaction, Publisher and Editorial Office

Instytut Kultury Fizycznej Uniwersytet Kazimierza Wielkiego w Bydgoszczy, Institute of Physical Education Kazimierz Wielki University in Bydgoszcz, Poland 85-091 Bydgoszcz ul. Sportowa 2  www.ukw.edu.pl Copyright by Instytut Kultury Fizycznej UKW w Bydgoszczy http://ojs.ukw.edu.pl/index.php/johs  Open Access ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

The journal has been approved for inclusion in ERIH PLUS.

The ERIH PLUS listing of the journal is available at https://dbh.nsd.uib.no/publiseringskanaler/erihplus/periodical/info?id=485984

SIC Science citation index (calculated on the basis of TCI and Page Rank) 0

Russian Impact factor 0.16

Indexed in Index Copernicus Journals Master List.

http://journals.indexcopernicus.com/Journal+of+Education+Health+and+Sport,p24782242,3.html

ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48

The InfoBase Index IBI Factor for the year 2015 is 3.56 in InfoBase Index.com.

Website: www.infobaseindex.com

Universal Impact Factor 1.78 for year 2012. (http://www.uifactor.org/AppliedJournals.aspx)

Indexed in Polish Scholarly Bibliography (PBN) (PBN Polska Bibliografia Naukowa) (https://pbn.nauka.gov.pl/journals/36616)

is a portal of the Polish Ministry of Science and Higher Education, collecting information on publications of Polish scientists and on Polish and foreign scholarly journals. Polish Scholarly Bibliograhpy is a part of POL-on - System of Information on Higher Education. It is operated by the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw.

Indexed in Russian Sciences Index Российский индекс научного цитирования (РИНЦ) http://elibrary.ru/contents.asp?titleid=37467

Indexed in Arianta Polish scientific and professional electronic journals Aneta Drabek i Arkadiusz Pulikowski

(http://www1.bg.us.edu.pl/bazy/czasopisma/czasop_full.asp?id=3595)