Status of Catalase, Glutathione Peroxidase, Glutathione S-Transferase, and Myeloperoxidase Gene Polymorphisms in Beta-Thalassemia Major Patients to Assess Oxidative Injury and Its Association with Enzyme Activities

Abstract

Beta-thalassemic patients require regular blood transfusion to sustain their life which leads to iron overload and causes oxidative stress. The aim of this study was to investigate the status of variants in genes including GSTM1, GSTT1 (null/present), CT-262 (C > T) and CT-89 (A > T), glutathione peroxidase (GPx), and myeloperoxidase (MPO). The genotype studies were conducted with 200 thalassemia major (TM) patients and 200 healthy controls. Genotyping of GST gene was performed by multiplex polymerase chain reaction (PCR), whereas for CT, GPx and MPO genesvariants PCR- restriction fragment length polymorphism technique used. However, the enzyme activities were measured only in the patients group to assess the association with the genotypes. All enzyme estimations were performed by ELISA. We observed higher frequency of GSTT1 null, CT-89 (A > T), GPx1 198 (C > T) and MPO-463 (G > A) polymorphisms in TM patient than healthy controls. However, CT-262 (C > T) polymorphism was not found to be statistically significantly different between patients and controls. Our results suggest that frequency of null allele of glutathione-S-transferase is significantly high among TM patients. The other alleles CT-89 (A > T), GPx1 198 (C > T), and MPO-463 (G > A) are linked to decreased CT, GPX, and MPO enzyme activities.

Keywords

thalassemia - glutathione-S-transferase - polymorphism - hemoglobin

Publication History

Received: 22 August 2020

Accepted: 16 December 2020

Article published online:
12 April 2021

• References

• 1 Bazvand F, Shams S, Borji Esfahani M. et al. Total antioxidant status in patients with major β-thalassemia. Iran J Pediatr 2011; 21 (02) 159-165
• 2 Amer J, Goldfarb A, Fibach E. Flow cytometric analysis of the oxidative status of normal and thalassemic red blood cells. Cytometry A 2004; 60 (01) 73-80
• 3 Amer J, Fibach E. Oxidative status of platelets in normal and thalassemic blood. Thromb Haemost 2004; 92 (05) 1052-1059
• 4 Abo-Shanab AM, El-Desouky MA, Kholoussi NM, El-Kamah GY, Helwa IA, Fahmi AA. The relation between glutathione S-Transferase M1 null-genotype and cardiac problems in beta-thalassemia. Acta Biochim Pol 2016; 63 (02) 267-271
• 5 Zhong SL, Zhou SF, Chen X. et al. Relationship between genotype and enzyme activity of glutathione S-transferases M1 and P1 in Chinese. Eur J Pharm Sci 2006; 28 (1-2): 77-85
• 6 Ogata M, Wang DH, Ogino K. Mammalian acatalasemia: the perspectives of bioinformatics and genetic toxicology. Acta Med Okayama 2008; 62 (06) 345-361
• 7 Crawford A, Fassett RG, Coombes JS. et al. Relationship between antioxidant enzyme genotype and activity and kidney function: a case-control study. Clin Nephrol 2012; 78 (02) 135-144
• 8 Forsberg L, Lyrenäs L, de Faire U, Morgenstern R. A common functional C-T substitution polymorphism in the promoter region of the human catalase gene influences transcription factor binding, reporter gene transcription and is correlated to blood catalase levels. Free Radic Biol Med 2001; 30 (05) 500-505
• 9 Franko A, Dolzan V, Arnerić N, Dodic-Fikfak M. Asbestosis and catalase genetic polymorphism. Arh Hig Rada Toksikol 2008; 59 (04) 233-240
• 10 Hong JR, Seok SJ, Jeong DS. et al. Association of the superoxide dismutase (V16A) and catalase (C262T) genetic polymorphisms with the clinical outcome of patients with acute paraquat intoxication. Korean J Intern Med (Korean Assoc Intern Med) 2010; 25 (04) 422-428
• 11 Miranda-Vilela AL, Alves PC, Akimoto AK. et al. Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study. Environ Health 2010; 9: 21
• 12 Mansego ML, Solar GdeM, Alonso MP. et al. Polymorphisms of antioxidant enzymes, blood pressure and risk of hypertension. J Hypertens 2011; 29 (03) 492-500
• 13 Arthur JR. The glutathione peroxidases. Cell Mol Life Sci 2000; 57 (13-14): 1825-1835
• 14 Mills GC. Glutathione peroxidase, an erythrocyte enzyme that protects hemoglobin from oxidative damage. J Biol Chem 1957; 229: 189-197
• 15 Moscow JA, Schmidt L, Ingram DT, Gnarra J, Johnson B, Cowan KH. Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer. Carcinogenesis 1994; 15 (12) 2769-2773
• 16 Winterbourn CC, Vissers MC, Kettle AJ. Myeloperoxidase. Curr Opin Hematol 2000; 7 (01) 53-58
• 17 Goedken M, McCormick S, Leidal KG. et al. Impact of two novel mutations on the structure and function of human myeloperoxidase. J Biol Chem 2007; 282 (38) 27994-28003
• 18 Piedrafita FJ, Molander RB, Vansant G, Orlova EA, Pfahl M, Reynolds WF. An Alu element in the myeloperoxidase promoter contains a composite SP1-thyroid hormone-retinoic acid response element. J Biol Chem 1996; 271 (24) 14412-14420
• 19 Pecoits-Filho R, Stenvinkel P, Marchlewska A. et al. A functional variant of the myeloperoxidase gene is associated with cardiovascular disease in end-stage renal disease patients. Kidney Int Suppl 2003; (84) S172-S176
• 20 Agarwal S, Gupta UR, Gambhir D, Pradhan M, Agarwal SS. B-thalassemia and hemoglobin variants in northern India: Determination of most common mutations. Br J Haematol 1998; 102: 46-46
• 21 Jafari M, Salimi S, Nakhaee A. et al. Lack of association between catalase gene C-262T polymorphism and systemic lupus erythematosus. Zahedan J Res Med Sci 2012; 14 (07) e93317
• 22 Lourdhu Mary A, Nithya K, Isabel W, Angeline T. Prevalence of catalase (-21 A/T) gene variant in south Indian (Tamil) population. BioMed Res Int 2014; 2014: 894237
• 23 Souiden Y, Mallouli H, Meskhi S. et al. MnSOD and GPx1 polymorphism relationship with coronary heart disease risk and severity. Biol Res 2016; 49: 22
• 24 Rajp A, Adu D, Savage CO. Meta-analysis of myeloperoxidase G-463/A polymorphism in anti-neutrophil cytoplasmic autoantibody-positive vasculitis. Clin Exp Immunol 2007; 149 (02) 251-256
• 25 Sultana S, Kolla K, Vidyullatha P. et al. Glutathione S- transferase M1 and T1 gene polymorphisms in South Indian stroke patients. Journal of Medical Genetics and Genomics 2011; 3 (04) 65-70 ISSN 2141–2278 ©2011 Academic Journals
• 26 Ellithy HN, Yousri S, Shahin GH. Relation between glutathione S-transferase genes (GSTM1, GSTT1, and GSTP1) polymorphisms and clinical manifestations of sickle cell disease in Egyptian patients. Hematology 2015; 20 (10) 598-606
• 27 Sanjay P, Mani MR, Sweta P, Vineet S, Kumar AR, Renu S. Prevalence of glutathione S-transferase gene deletions and their effect on sickle cell patients. Rev Bras Hematol Hemoter 2012; 34 (02) 100-102
• 28 Cheng TY, Barnett MJ, Kristal AR. et al. Genetic variation in myeloperoxidase modifies the association of serum α-tocopherol with aggressive prostate cancer among current smokers. J Nutr 2011; 141 (09) 1731-1737
• 29 Finkel T. Oxidant signals and oxidative stress. Curr Opin Cell Biol 2003; 15 (02) 247-254
• 30 Bostwick DG, Alexander EE, Singh R. et al. Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer. Cancer 2000; 89 (01) 123-134
• 31 Bănescu C, Trifa AP, Voidăzan S. et al. CAT, GPX1, MnSOD, GSTM1, GSTT1, and GSTP1 genetic polymorphisms in chronic myeloid leukemia: a case-control study. Oxid Med Cell Longev 2014; 2014: 875861
• 32 Nagy T, Csordás M, Kósa Z, Góth L. A simple method for examination of polymorphisms of catalase exon 9: rs769217 in Hungarian microcytic anemia and beta-thalassemia patients. Arch Biochem Biophys 2012; 525 (02) 201-206
• 33 Skakir ZH, Lawi ZKK, Lateef GR. Investigation of catalase gene polymorphisms in patients with thalassima in hilla city. Biochem Cell Arch 2019; 19 (Suppl. 01) 2495-2497
• 34 Holben DH, Smith AM. The diverse role of selenium within selenoproteins: a review. J Am Diet Assoc 1999; 99 (07) 836-843
• 35 Livrea MA, Tesoriere L, Pintaudi AM. et al. Oxidative stress and antioxidant status in beta-thalassemia major: iron overload and depletion of lipid-soluble antioxidants. Blood 1996; 88 (09) 3608-3614
• 36 Loebstein R, Lehotay DC, Luo X, Bartfay W, Tyler B, Sher GD. Diabetic nephropathy in hypertransfused patients with beta-thalassemia. The role of oxidative stress. Diabetes Care 1998; 21 (08) 1306-1309
• 37 Bartfay WJ, Bartfay E. Selenium and glutathione peroxidase with beta-thalassemia major. Nurs Res 2001; 50 (03) 178-183
• 38 Patne AB, Hisalkar P, Gaikwad SB, Patil SV. Alterations in antioxidant enzyme status with lipid peroxidation in β thalassemia major patients. Int J Pharm & Life Sci 2012; 3 (10) 2003-2006 (IJPLS) ISSN: 0976–7126
• 39 Anatoliotakis N, Deftereos S, Bouras G. et al. Myeloperoxidase: expressing inflammation and oxidative stress in cardiovascular disease. Curr Top Med Chem 2013; 13 (02) 115-138
• 40 Yahouédéhou SCMA, Carvalho MOS, Oliveira RM. et al. Sickle cell anemia patients in use of hydroxyurea: association between polymorphisms in genes encoding metabolizing drug enzymes and laboratory parameters. Dis Markers 2018; 2018: 6105691
• 41 Bozina N, Bradamante V, Lovrić M. Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol 2009; 60 (02) 217-242