HEMATOLOGY / CLINICAL RESEARCH
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Studies in beta thalassaemia major (β-TM) patients have shown that the responses of HIF2α, hepcidin, and ferroportin molecules to high iron levels are impaired. In recent years, studies conducted in patients with iron deficiency anaemia have investigated the relationship between ghrelin hormone and iron metabolism. In this study, we aimed to contribute to the aetiopathogenesis of this disease by examining the changes in ghrelin hormone levels in patients with β-TM.

Material and methods:
Fifty-two β-TM and 23 controls were included in our study. Blood counts, routine biochemical parameters, HIF2α, hepcidin, and ghrelin levels were studied in blood samples taken from the volunteers.

Results:
Erythrocyte indexes, serum bilirubin, iron, unsaturated iron binding capacity, total iron binding capacity, and ferritin levels showed significant differences between the 2 groups (p < 0.05). There was no significant difference between 2 groups for serum HIF2α and hepcidin levels. When the 2 groups were compared, ghrelin levels were found to be significantly higher in the patients (p < 0.05). When the correlation between parameters was examined in all subjects, a weak positive correlation was found between ghrelin and HIF2α (r = 0.263) (p < 0.05), and a significant positive correlation was found between ghrelin and ferritin (r = 0.417) (p < 0.05).

Conclusions:
Our study showed that there is a positive correlation between ghrelin and ferritin levels. Elevated ghrelin levels in patients with β-TM may play an important role in regulating impaired iron metabolism. Molecular level studies are needed to determine synthesis pathways.

 
REFERENCES (43)
1.
Nemeth E, Ganz T. Hepcidin-ferroportin interaction controls systemic iron homeostasis. Int J Mol Sci 2021; 22: 6493.
 
2.
Vogt AS, Arsiwala T, Mohsen M, et al. On iron metabolism and its regulation. Int J Mol Sci 2021; 22: 4591.
 
3.
Baird DC, Batten SH, Sparks SK. Alpha- and beta-thalassemia: rapid evidence review. Am Fam Physician 2022; 105: 272-80.
 
4.
Gupta D, Patterson AM, Osborne-Lawrence S, et al. Disrupting the ghrelin-growth hormone axis limits ghrelin’s orexigenic but not glucoregulatory actions. Mol Metab 2021; 53: 101258.
 
5.
Song X, Wang M, Jiao H, et al. Ghrelin is a signal to facilitate the utilization of fatty acids and save glucose by the liver, skeletal muscle, and adipose tissues in chicks. Biochim Biophys Acta Mol Cell Biol Lipids 2022; 1867: 159081.
 
6.
Ghrayeb H, Elias M, Nashashibi J, et al. Appetite and ghrelin levels in iron deficiency anemia and the effect of parenteral iron therapy: a longitudinal study. PLoS One 2020; 15: e0234209.
 
7.
Kucuk N, Orbak Z, Karakelloglu C, Akcay F. The effect of therapy on plasma ghrelin and leptin levels, and appetite in children with iron deficiency anemia. J Pediatr Endocrinol Metab 2019; 32: 275-80.
 
8.
Moshtaghi-Kashanian GR, Razavi F. Ghrelin and leptin levels in relation to puberty and reproductive function in patients with beta-thalassemia. Hormones 2009; 8: 207-13.
 
9.
Luo QQ, Zhou YF, Chen MYJ, et al. Fasting up-regulates ferroportin 1 expression via a Ghrelin/GHSR/MAPK signaling pathway. J Cell Physiol 2018; 233: 30-7.
 
10.
Sundh A, Kaur P, Palta A, Kaur G. Utility of screening tools to differentiate beta thalassemia trait and iron-deficiency anemia – do they serve a purpose in blood donors? Blood Res 2020; 55: 169-74.
 
11.
Khandros E, Kwiatkowski JL. Beta thalassemia: monitoring and new treatment approaches. Hematol Oncol Clin North Am 2019; 33: 339-53.
 
12.
Hasan D, Al Tibi A, Burghel G, et al. Determining the current prevalence of -thalassemia variants in Jordan. Arch Med Sci 2023; 19: 523-7.
 
13.
Tubman VN, Fung EB, Vogiatzi M, et al. Guidelines for the standard monitoring of patients with thalassemia. J Pediatr Hematol Oncol 2015; 37: e162-9.
 
14.
Kattamis A, Kwiatkowski JL, Aydinok Y. Thalassaemia. Lancet 2022; 399: 2310-24.
 
15.
Sultana I, Sultana N, Rabbany MA, et al. Faysal MR. evaluation of liver function tests in -thalassemia major children. Mymensingh Med J 2022; 31: 894-9.
 
16.
Gao J, Liu W. Advances in screening of thalassaemia. Clin Chim Acta 2022; 534: 176-84.
 
17.
Bansal D, Lal A. Iron metabolism, hemolytic anemia, and thalassemia. Indian J Pediatr 2020; 87: 56-7.
 
18.
Kwiatkowski JL. Clinical challenges with iron chelation in beta thalassemia. Hematol Oncol Clin North Am 2023; 37: 379-91.
 
19.
Pinto VM, Forni GL. Management of iron overload in beta-thalassemia patients: clinical practice update based on case series. Int J Mol Sci 2020; 21: 8771.
 
20.
Chauhan W, Shoaib S, Fatma R, et al. Beta-thalassemia and the advent of new interventions beyond transfusion and iron chelation. Br J Clin Pharmacol 2022; 88: 3610-26.
 
21.
Mahroum N, Alghory A, Kiyak Z, et al. Ferritin – from iron, through inflammation and autoimmunity, to COVID-19. J Autoimmun 2022; 126: 102778.
 
22.
Plays M, Müller S, Rodriguez R. Chemistry and biology of ferritin. Metallomics 2021; 13: mfab021.
 
23.
Estevão IF, Peitl J, Bonini-Domingos CR. Serum ferritin and transferrin saturation levels in 0 and  + thalassemia patients. Genet Mol Res 2011; 10: 632-9.
 
24.
Hsu CC, Senussi NH, Fertrin KY, Kowdley KV. Iron overload disorders. Hepatol Commun 2022; 6: 1842-54.
 
25.
Rujeerapaiboon N, Tantiworawit A, Piriyakhuntorn P, et al. Correlation between serum ferritin and viral hepatitis in thalassemia patients. Hemoglobin 2021; 45: 175-9.
 
26.
Tantiworawit A, Khemakapasiddhi S, Rattanathammethee T, et al. Correlation of hepcidin and serum ferritin levels in thalassemia patients at Chiang Mai University Hospital. Biosci Rep 2021; 41: BSR20203352.
 
27.
Agarwal AK, Yee J. Hepcidin. Adv Chronic Kidney Dis 2019; 26: 298-305.
 
28.
Czempik PF, Wiórek A. Iron deficiency in sepsis patients based on reticulocyte hemoglobin and hepcidin concentration: a prospective cohort study. Arch Med Sci 2023; 19: 805-9.
 
29.
Fibach E, Dana M. Oxidative stress in -thalassemia. Mol Diagnosis Ther 2019; 23: 245-61.
 
30.
Srole DN, Ganz T. Erythroferrone structure, function, and physiology: iron homeostasis and beyond. J Cell Physiol 2021; 236: 4888-901.
 
31.
Ali S, Mumtaz S, Shakir HA, et al. Current status of beta-thalassemia and its treatment strategies. Mol Genet Genomic Med 2021; 9: e1788.
 
32.
Pagani A, Nai A, Silvestri L, Camaschella C. Hepcidin and anemia: a tight relationship. Front Physiol 2019; 10: 1294.
 
33.
Preza GC, Ruchala P, Pinon R, et al. Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload. J Clin Invest 2011; 121: 4880-8.
 
34.
Casu C, Oikonomidou PR, Chen H, et al. Minihepcidin peptides as disease modifiers in mice affected by -thalassemia and polycythemia vera. Blood 2016; 128: 265-76.
 
35.
Xu MM, Wang J, Xie JX. Regulation of iron metabolism by hypoxia-inducible factors. Sheng Li Xue Bao 2017; 69: 598-610.
 
36.
Ban HS, Uto Y, Nakamura H. Hypoxia-inducible factor (HIF) inhibitors: a patent survey (2016–2020). Expert Opin Ther Pat 2021; 31: 387-97.
 
37.
Mastrogiannaki M, Matak P, Delga S, et al. Deletion of HIF-2 in the enterocytes decreases the severity of tissue iron loading in hepcidin knockout mice. Blood 2012; 119: 587-90.
 
38.
Schwartz AJ, Das NK, Ramakrishnan SK, et al. Hepatic hepcidin/intestinal HIF-2 axis maintains iron absorption during iron deficiency and overload. J Clin Invest 2019; 129: 336-48.
 
39.
Anderson ER, Taylor M, Xue X, et al. Intestinal HIF2 promotes tissue-iron accumulation in disorders of iron overload with anemia. Proc Natl Acad Sci USA 2013; 110: E4922-30.
 
40.
Isguven P, Arslanoglu I, Erol M, et al. Serum levels of ghrelin, leptin, IGF-I, IGFBP-3, insulin, thyroid hormones and cortisol in prepubertal children with iron deficiency. Endocr J 2007; 54: 985-90.
 
41.
Akarsu S, Ustundag B, Gurgoze MK, et al. Plasma ghrelin levels in various stages of development of iron deficiency anemia. J Pediatr Hematol Oncol 2007; 29: 384-7.
 
42.
Dogan A, Alioglu B, Dindar N, Dallar Y. Increased serum hepcidin and ghrelin levels in children treated for iron deficiency anemia. J Clin Lab Anal 2013; 27: 81-5.
 
43.
Karamifar H, Bahmanyar M, De Sanctis V, Karimi M. Leptin and ghrelin serum concentrations in thalassemia major and intermedia patients and normal subjects. Riv Ital di Med dell’Adolescenza 2010; 8: 29-33.
 
eISSN:1896-9151
ISSN:1734-1922
Journals System - logo
Scroll to top