Lviv clinical bulletin 2020, 2(30): 14-20

Structural and Functional Peculiarities of Cardiac Changes in Non-Alcoholic Fatty Liver Disease Patients With Different Polymorphic Variants of the Deletion Polymorphism of the Glutathione-S-Transferase M1 Gene

V. Prysyazhnyuk, T. Ilashchuk, L. Sydorchuk, P. Prysyazhnyuk, K. Bobkovych, N. BachukPonych

Bukovinian State Medical University

Introduction. Epidemiological studies indicate a higher incidence of adverse cardiovascular events in patients with non-alcoholic fatty liver disease (NAFLD) as compared to the general population. In the case of a comorbid combination of liver and cardiovascular diseases, the natural course of cardiovascular pathology may be different even in patients with similar liver changes, indicating that this differences may be genetically determined.

The aim of this study.  To find out structural and functional peculiarities of cardiac changes in non-alcoholic fatty liver patients disease with different polymorphic variants of the deletion polymorphism of the glutathione-S-transferase M1 gene.

Materials and methods. The study included 104 NAFLD patients and 45 healthy individuals (control group). First group included 52 patients without deletion of the GSTM1 gene, second group consisted of 52 patients with deletion of the GSTM1 gene. All patients and practically healthy people were performed with objective examination, determination of anthropometric parameters, general and biochemical blood tests, ultrasonographic examination of abdominal organs, elastography of the liver, echocardiographic investigation, investigation of the GSTM1 gene deletion polymorphism.

Results. The distribution of polymorphic variants of the deletion polymorphism GSTM1 among NAFLD patients did not differ from healthy individuals. In patients with deletion variant of the GSTM1 gene, a larger diameter of the left atrium was noted by 0.34 cm (8.3 %, p = 0.007), end diastolic size of the left ventricle by 0.42 cm (7.9 %, p = 0.02) and end systolic size by 0.44 cm (12.5 %, p = 0.02) end diastolic volume by 23.2 % (p = 0.03) end systolic volume by 34.5 % (p = 0.04) left ventricular myocardial mass by 16.4 % (p = 0.03) as compared to the corresponding values in patients without deletion of the GSTM1 gene. For female patients with GSTM1 (-) a greater left ventricular myocardial mass index by 24.6 % (p = 0.02) was characteristic in comparison with female patients with GSTM (+). Eccentric hypertrophy was detected in 24.0 % of patients of the first group and 44.0 % of patients of the second group as a result of calculating the type of geometric configuration of the left ventricle myocardium. Concentric hypertrophy was diagnosed in 76.0 % and 52.0 % of patients, respectively, and concentric remodeling of left ventricle was detected in 4.0 % of patients in the second group. The likelihood of type of myocardial hypertrophy depending on the polymorphic variant of the GSTM1 gene was not significantly different, we note only a tendency to increase the number of patients with concentric hypertrophy in the first group and those with eccentric hypertrophy in the second group.

Conclusions. Conducted studies have shown that non-alcoholic fatty liver disease patients with different polymorphic variants of the deletion polymorphism of the glutathione-S-transferase M1 gene are characterized by different structural and functional changes of the heart. The distribution of polymorphic variants of the glutathione-S-transferase M1 gene is not significantly different in patients with non-alcoholic fatty liver disease and healthy individuals. Deletion genotype of the glutathione-S-transferase M1 gene in non-alcoholic fatty liver disease patients is associated with larger diameter of the left atrium, end systolic and diastolic sizes and volumes of the left ventricle, left ventricular myocardium mass, and in female patients also left ventricle myocardium mass index as compared to the corresponding indicators in patients without deletion of the gene functional allele.


  1. Kolesnikova OV. Relationship between the severity of non-alcoholic liver steatosis and major metabolic parameters in patients at high cardiovascular risk. Bukovinian Medical Herald. 2012;16(1):36-41 (Ukrainian).
  2. Ministry of Health of Ukraine Order No. 826 dated 06.11.2014 “On approval and implementation of medical and technological documents on standardization of medical care in chronic non-communicable hepatitis”. Kyiv: Ministry of Health; 2014. (Ministry of Health of Ukraine normative document  (Ukrainian).
  3. Order of the Ministry of Health of Ukraine and AMS of Ukraine N 641/84 of 31.12.2003 “On Improvement of Medical Genetic Assistance in Ukraine”. Kyiv: Ministry of Health; 2004. (Ministry of Health of Ukraine normative document  (Ukrainian).
  4. Oparin AA, Oparin AG, Fedchenko YuG, Blagoveshhenskaya AV. Ultrasound examination of the liver is normal and pathological. Eastern European Journal of Internal and Family Medicine. 2016;2:43-54 (Russian)
  5. Sirenko YuM. Injury of the heart in hypertension. Ukrainian Cardiology Journal. 2007;1:50-52 (Ukrainian).
  6. Asmi MN, Walsh MJ. A Practical Guide to Echocardiograpthy. London: Chapman and Hall Medical; 1995. 260 p.
  7. Capoluongo E, Onder G, Concolino P, Russo A, Santonocito C, Bernabei R et al. GSTM1-null polymorphism as possible risk marker for hypertension: results from the aging and longevity study in the Sirente Geographic Area (ilSIRENTE study). Clin Chim Acta. 2009;399(1-2):92-0
  8. Cuspidi C, Sala C, Negri F, Mancia G, Morganti A Prevalence of left-ventricular hypertrophy in hypertension: an updated review of echocardiographic studies. J Hum Hypertens. 2012;26(6):343-349.
  9. Eslami S, Sahebkar A. Glutathione-S-transferase M1 and T1 null genotypes are associated with hypertension risk: a systematic review and meta-analysis of 12 studies. Curr Hypertens Rep. 2014;16(6):432.
  10. Ganau A, Devereux RB, Roman MJ, de Simone G, Pickering TG, Saba PS et al. Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. J Am Coll Cardiol. 1992;19(7):1550-1558.
  11. Huang L, Li L, Hu E, Chen G, Meng X, Xiong C et al. Potential biomarkers and targets in reversibility of pulmonary arterial hypertension secondary to congenital heart disease: an explorative study. Pulm Circ. 2018;8(2):2045893218755987.
  12. Hurjui DM, Niţă O, Graur LI, Mihalache L, Popescu DS, Huţanaşu IC et al. Non-alcoholic fatty liver disease is associated with cardiovascular risk factors of metabolic syndrome. Rev Med Chir Soc Med Nat Iasi. 2012;116(3):692-699.
  13. Ikeda Drug-induced idiosyncratic hepatotoxicity: prevention strategy developed after the troglitazone case. Drug Metab Pharmacokinet. 2011;26(1):60-70.
  14. Lakhdar R, Denden S, Knani J, Leban N, Daimi H, Hassine M, et al. Relationship between glutathione S-transferase P1 polymorphisms and chronic obstructive pulmonary disease in a Tunisian population. Genet Mol Res. 2010;9(2):897-907.
  15. Lee DH, Silventoinen K, Hu G, Jacobs DR Jr, Jousilahti P, Sundvall J, et al. Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women. Eur Heart J. 2006;27(18):2170-2176.
  16. Lucena MI, Andrade RJ, Martínez C, Ulzurrun E, García-Martín E, Borraz Y, et al. Glutation-S-transferase m1 and t1 null genotypes increase susceptibility to idiosyncratic drug-induced liver injury. Hepatology. 2008;48(2):588-596.
  17. Maciel SS, Pereira Ada C, Silva GJ, Rodrigues MV, Mill JG, Krieger JE. Association between glutathione S-transferase polymorphisms and triglycerides and HDL-cholesterol. Atherosclerosis. 2009;206(1):204-208.
  18. Marchesini G, Day ChP, Dufour JF, Canbay A, Nobili V, Ratziu V et al. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-1402.
  19. Motamed N, Rabiee B, Poustchi H, Dehestani B, Hemasi GR, Khonsari MR et al. Non-alcoholic fatty liver disease (NAFLD) and 10-year risk of cardiovascular diseases. Clin Res Hepatol Gastroenterol. 2017;41(1):31-38.
  20. Prysyazhnyuk Age-dependent peculiarities of echocardiographic parameters of the heart in patients with nonalcoholic fatty liver disease. Bukovinian Medical Herald. 2014;18(4):116-119.
  21. Savolainen VT, Pjarinen J, Perola M, Penttilä A, Karhunen PJ. Glutathione-S-transferase GST M1 ″null″ genotype and the risk of alcoholic liver disease. Alcohol Clin Exp Res. 1996;20(8):1340-1345.
  22. Takeuchi Y, Ito H, Komatsu Y, Oshikiri K, Antoku S, Abe M et al. Non-alcoholic Fatty Liver Disease is an Independent Predictor for Macroangiopathy in Japanese Type 2 Diabetic Patients: A Cross-sectional Study. Intern Med. 2012;51(13):1667-1775.
  23. Treeprasertsuk S, Leverage S, Adams LA, Lindor KD, St Sauver J, Angulo P. The Framingham risk score and heart disease in nonalcoholic fatty liver disease. Liver Int. 2012;32(6):945-950.
  24. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018;39:3021-3104.
  25. Zhang ZX, Zhang Y. Glutathione S-transferase M1 (GSTM1) null genotype and coronary artery disease risk: a meta-analysis. Int J Clin Exp Med. 2014;15;7(10):3378-3384.