Exon 2 Vitamin D Receptor (Fok-I) Gene Polymorphism and the Evaluation of its Correlation With Renal Dysfunction in Patients With β-Thalassemia Major in East Azerbaijan Province of Iran

Introduction It is approved that thalassemia is one of the most prominent single-gene abnormalities. This disorder leads to a kind of microcytic-hypochromic anemia which is originated from the inherited impairment of hemoglobin synthesis and thus lowers the erythrocyte life span (1). In addition, beta-thalassemia is more common than alphathalassemia in Iran (2). Currently, the quality of life for thalassemic patients is increasingly improved with the use of newborn screening, regular blood transfusion, and effective treatment. However, there are a quite number of difficulties (2,3), one of which is the iron overload that is the most fundamental issue (4). Renal dysfunctions associated with beta-thalassemia major was first reported in 1975 (5). Several renal abnormalities in beta-thalassemic patients were illuminated comprising the up-regulation of the stream of renal plasma, urine concentration impairment, renal tubular acidosis, and tubulopathies (3,4,6). Many studies have approved renal disorders in beta-thalassemia although the exact mechanisms of this phenomenon are not clarified completely (7). Vitamin D in active species with parathyroid hormone rises the reabsorption of calcium (Ca) from the kidney. Previous research on thalassemia patients showed that vitamin D deficiency occurred in these patients (8). Most of the physiological actions of vitamin D is done via connecting to specific intracellular receptors. Further, the occurrence of single nucleotide polymorphism) in vitamin D receptor (VDR) could potentially modify the transcriptional activities of the target genes (9,10). Furthermore, VDR polymorphisms can occur in the 5’ promoter, 3’ untranslated region, and exonic sequences. The restriction fragment length polymorphism (RFLP) method, which is done on the VDR gene, has shown a variety of Abstract Objectives: Several studies have shown that major beta-thalassemia patients suffer from renal dysfunction. Genetic is one of the crucial factors in this phenomenon. Accordingly, this study aimed to evaluate the correlation between renal dysfunction and Fok-I polymorphism in the vitamin D receptor (VDR) gene of major beta-thalassemia patients. Materials and Methods: Sixty thalassemic patients and sixty healthy individuals were involved in this case-control study. Robust renal and urine analyzes were done in terms of performance evaluation. Finally, genotype assessment for Fok-I polymorphism was performed via the polymerase chain reaction-restriction fragment length polymorphism method. Results: In general, renal dysfunction embracing proteinuria and hyperfilteration were observed in the thalassemic group. As regards patients’ genotype frequencies, 51.6%, 36.6%, and 11.6% were homozygous for F allele (FF), heterozygous (Ff), and homozygous for f allele (ff), respectively. Eventually, the frequencies of FF and Ff alleles were 49.1% and 50.8%, respectively, in normal group l. Conclusions: Our data suggested that there is no correlation between renal dysfunction and Fok-I polymorphism in major betathalassemic patients. Thus, further studies are needed about plausible pathways involved in renal dysfunction, to demonstrate the motives of renal dysfunction in major beta-thalassemia patients.