Main Article Content
Thalassemia, a monogenic genetic disease of red blood cells, is spread widely throughout the world. Glutathione S transferase (GST) enzymes have an antioxidant role in detoxification processes of toxic substances This study aimed to determine the role of the genetic modifier genes GSTT1 and GSTM1, and the catalase (CAT) gene in clinical degrees of hemoglobin (Hb)E/β thalassemia.
Sixty HbE/β Thalassemia patients were examined to determine their clinical pictures. Clinical score was based on age when thalassemia symptoms appeared, time of diagnosis, time of first blood transfusion, pre-transfusion hemoglobin concentration, frequency of transfusions, and enlargement of spleen. Ferritin concentration was also obtained from medical records. Gene polymorphisms of GSTT1, GSTM1, and CAT were measured using PCR and PCR-RFLP methods. Clinical scores were categorized into mild (0-3.5), moderate (4-7), and severe (7.5-10) degrees, while ferritin level was expressed in mg/dL. One way Anova was used to analyze the data.
The clinical appearance showed that severe, moderate, and mild degrees accounted for 42%, 45%, and 13%, respectively. The majority had a high ferritin level of more than 5000 mg/dL (67%). GSTT1 null, GSTM1 null, and CAT minor allele genotypes were 21.7%, 33.3%, and 12.1%, respectively. GSTT1, GSTM1, and CAT genotypes had no impact on the severity of thalassemia patients (p=0.091, p=0.082, and p=0.141, respectively).
GSTT1, GSTM1, CAT gene polymorphisms tend to be a minor aspect of severity of clinical outcome for HbE/â thalassemia patients and should be not considered a routine laboratory check.
The journal allows the authors to hold the copyright without restrictions and allow the authors to retain publishing rights without restrictions.
Rujito L, Basalamah M, Siswandari W, et al. Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances: a study on â-thalassemia and hemoglobin E/â-thalassemia patients in Indonesia. Hematol Oncol Stem Cell Ther 2016;9:55-63. doi: 10.1016/j.hemonc.2016.02. 003.
Hahn T, Zhelnova E, Sucheston L, et al. A deletion polymorphism in glutathione-S-transferase mu (GSTM1) and/or theta (GSTT1) is associated with an increased risk of toxicity after autologous blood and marrow transplantation. Biol Blood Marrow Transpl 2010;16:801–8. doi: 10.1016/j.bbmt.2010.01.001.
Sclafani S, Calvaruso G, Agrigento V, Maggio A, Lo Nigro V, D’Alcamo E. Glutathione S transferase polymorphisms influence on iron overload in â-thalassemia patients. Thalass Reports 2013;3:e6. DOI: https://doi.org/10.4081/thal.2013.e6.
Origa R, Satta S, Matta G, Galanello R. Glutathione S-transferase gene polymorphism and cardiac iron overload in thalassaemia major. Br J Haematol 2008;142:143–5. doi: 10.1111/j.1365-2141.2008. 07175.x.
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;525:201–6.
Sripichai O, Makarasara W, Munkongdee T, et al. A scoring system for the classification of beta-thalassemia/Hb E disease severity. Am J Hematol 2008;83:482–4.
Traivaree C, Monsereenusorn C, Rujkijyanont P, Prasertsin W, Boonyawat B. Genotype -phenotype correlation among beta-thalassemia and beta-thalassemia/HbE disease in Thai children: predictable clinical spectrum using genotypic analysis. J Blood Med 2018;9:35-41. doi: 10.2147/jbm.s159295.
Ruangrai W, Jindadamrongwech S. Genetic factors influencing hemoglobin F level in Beta-thalassenia/HbE disease. Southeast Asian J Trop Med Public Health 2016;47:84–91.
Cao A, Galanello R, Origa R. Beta-thalassemia. Genet Med 2010;12:61-76. doi: 10.1097/GIM. 0b013e3181cd68ed.
Thein SL. Molecular basis of â thalassemia and potential therapeutic targets. Blood Cells Mol Dis 2018;70:54-65. doi: 10.1016/j.bcmd.2017.06.001.
Rujito L, Sasongko T. Genetic background of â thalassemia modifier: recent update. J Biomed Translational Res 2018;4:12-21. https://doi.org/10.14710/jbtr.v4i1.2541
Kasthurinaidu SP, Ramasamy T, Ayyavoo J, Dave DK, Adroja DA GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach. PLoS One 2015;10:e0118660. doi: 10.1371/journal.pone. 0118660.10:e0118660.
Dou H, Qin Y, Chen G, Zhao Y. Effectiveness and safety of deferasirox in thalassemia with iron overload: a meta-analysis. Acta Haematol 2019;141:32-42. doi: 10.1159/000494487.
Sharma V, Kumar B, Saxena R. Glutathione S-transferase gene deletions and their effect on iron status in HbE/â thalassemia patients. Ann Hematol 2010;89:411–4.
Cao A, Moi P, Galanello R. Recent advances in beta-thalassemias. Pediatr Rep 2011;3:e17. doi: 10.4081/pr.2011.e17.
Nasr A, Sami R, Ibrahim N, Darwish D. Glutathione S transferase (GSTP 1, GSTM 1, and GSTT 1) gene polymorphisms in Egyptian patients with acute myeloid leukemia. Indian J Cancer 2015;52:490–5.
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;34:100–2.
Meloni A, Puliyel M, Pepe A, Berdoukas V, Coates TD, Wood JC. Cardiac iron overload in sickle-cell disease. Am J Hematol 2014;89:678-83. doi: 10.1002/ajh.23721.
Ozturk Z, Genc GE, Kupesiz A, Kurtoglu E, Gumuslu S. Thalassemia major patients using iron chelators showed a reduced plasma thioredoxin level and reduced thioredoxin reductase activity, despite elevated oxidative stress. Free Radic Res 2015;49:309-16. doi: 10.3109/10715762.2015. 1004327.
Van Zwieten R, Verhoeven AJ, Roos D. Inborn defects in the antioxidant systems of human red blood cells. Free Radic Biol Med 2014;67:377-86. doi: 10.1016/j.freeradbiomed.2013.11.022.
Góth L, Nagy T, Kósa Z, et al. Effects of rs769217 and rs1001179 polymorphisms of catalase gene on blood catalase, carbohydrate and lipid biomarkers in diabetes mellitus. Free Radic Res 2012;46:1249–57.
Liu Y, Xie L, Zhao J, et al. Association between catalase gene polymorphisms and risk of chronic hepatitis B, hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma in Guangxi population: a case-control study. Medicine (Baltimore) 2015;94:e702. doi: 10.1097/MD. 0000000000000702.
Chioti V, Zervoudakis G. Is root catalase a bifunctional catalase-peroxidase? Antioxidants 2017;6:39. doi: 10.3390/antiox6020039.
Lazarte SS, Mónaco ME, Jimenez CL, Achem MEL, Terán MM, Issé BA. Erythrocyte catalase activity in more frequent microcytic hypochromic anemia: Beta-thalassemia trait and iron deficiency anemia. Adv Hematol 2015;2015. Article ID 343571. doi: 10.1155/2015/343571.
Madhikarmi NL, Rudraiah K, Murthy S. Antioxidant enzymes and oxidative stress in the erythrocytes of iron deficiency anemic patients supplemented with vitamins. Iran Biomed J Iran Biomed J 2014;18:82-7. doi: 10.6091/ibj.12282.2013
Yamsri S, Singha K, Prajantasen T, et al. A large cohort of beta(+)-thalassemia in Thailand: Molecular, hematological and diagnostic considerations. Blood Cells Mol Dis 2015;54:164-9. doi: 10.1016/j.bcmd.2014.11.008.