Relationship of levels of transforming growth factor-beta1 (TGF-β1) to the levels of ferritin in blood of transfusion dependent β-thalassemia major patients with growth retardation: A case-control study

Abstract

Introduction: Transforming growth factor-beta (TGF-β) is a pleiotropic polypeptide member of the TGF-β superfamily of cytokines that has multicellular functions. Thalassemias are the most common genetic disorder worldwide. Severe forms are termed thalassemia major characterized by repeated blood transfusions with the elevation of iron levels and progressive multi-organ failure mainly involving endocrine glands and other major organs. It is common to find stunted growth in advanced cases especially among teenage patients. Ferritin is an iron-binding protein can store iron in a safe formula that reflects iron state; conversely, the free-iron concentrations can control intracellular ferritin levels. Serum ferritin is a valuable monitoring marker for iron-overload in thalassemias. This study is designed to assess the relationship of levels ferritin to the TGF-β1 in the sera of β-thalassemia patients and their association to growth retardation. Materials and methods: This is a cross-sectional study included 196 subjects; 147 children identified as β- thalassemia major and 49 healthy controls. The thalassemic patients were on consistent follow-up, had received repeated blood transfusions and on iron-chelation therapy. The forty-nine healthy control group were free of any blood disorders or growth abnormalities. The height, weight, and BMI of the studied groups were compared on both standards from WHO and CDC growth charts to evaluate their growth status. In accordance with their growth, the patients were stratified into three groups: those with mild growth impairment, stunted growth, and normal growth groups. Moreover, all subjects’ sera concentrations of both ferritin and TGF-β1 were evaluated. Results: The mean age showed no significant differences among the 4 groups. The male: female ratio, as well as BMI, were nearly the same amongst the study groups despite both height and weight were significantly differed between normal thalassemics and controls. There were no definite impression of gender on the distribution of ferritin and TGF-β1 individually among the involved subjects. There was a significant correlation of both mean serum ferritin and TGF-β1 mutually, with the four groups being higher in mild and stunted growth patients (2142 ng/ml & 271.3 pg/dl) and lower in normal thalassemics (1005 ng/ml & 76.9 pg/dl) and control group (60.6 ng/ml and 291.7 pg/dl) consequently. The mean ferritin and TGF-β1 levels were significantly correlated only among stunted thalassemics even with levels of ferritin higher than 1000ng/dl. The analysis of linear-regression revealed significant strength of the relationship between levels of ferritin with TGF-β1 in sera of mild and stunted growth patients, while there was a poor insignificant relationship in normal thalassemics and controls. The correlations of ferritin and TGF-β1 with height ZScore and weight ZScore were significant together in 1st and 2nd groups of thalassemia, on the other hand, it was insignificant among third and fourth groups apart from their correlation with height ZScore. Conclusions: 1-thalassemia with mild and stunted growth show higher serum levels of TGF-β1 and ferritin than normal thalassemia and healthy subjects. 2-Higher TGF-β1 levels in thalassemics might be an extraordinary cause of disturbing iron metabolism, expressed by elevated serum ferritin levels. 3- Higher TGF-β1 levels correlate well with growth stunting in thalassemic patients.

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