Fok-I Polymorphism of Vitamin D Receptor Gene and the Presence of Renal Dysfunction in Patients with β-Thalassemia Major

• Published in: Pediatric hematology and oncology 2011-09, Vol.28 (6), p.509-516
• Main Authors: Dimitriadou, Meropi, Christoforidis, Athanasios, Economou, Marina, Teli, Aikaterini, Printza, Nikoleta, Tzimouli, Vasiliki, Tsatra, Ioanna, Fidani, Liana, Papachristou, Fotis, Athanassiou-Metaxa, Miranda
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; beta 2-Microglobulin - urine; beta-Thalassemia - blood; beta-Thalassemia - genetics; beta-Thalassemia - urine; Biomarkers - blood; Biomarkers - urine; Calcium - urine; Child; Child, Preschool; cystatin C; Cystatin C - blood; Female; Fok-I polymorphism; Gene Frequency; Genotype; Glomerular Mesangium - metabolism; Humans; Kidney Diseases - blood; Kidney Diseases - genetics; Kidney Diseases - urine; Male; Polymorphism, Restriction Fragment Length; Proteinuria - blood; Proteinuria - urine; Receptors, Calcitriol - genetics; Receptors, Calcitriol - metabolism; renal function; thalassemia; vitamin D receptor
• ISSN: 0888-0018; 1521-0669
• DOI: 10.3109/08880018.2011.579231

Recent evidence supports the presence of renal dysfunction even among young patients with β-thalassemia major. However, the possible genetic contribution has never been investigated. The aim of this study was to correlate the presence of Fok-I polymorphism of the vitamin D receptor gene with abnormal levels of early markers of renal impairment in children and young adults with thalassemia. Thirty-four patients (19 male and 15 female) with β-thalassemia major on conventional treatment, with a mean decimal age of 14.62 ± 5.47 years (range: 5-22 years), were included in the study. Markers of renal function were determined in serum and in urine and patients were genotyped for Fok-I gene polymorphism. Genotype frequencies were similar to those previously reported for other populations: 47.06% of the patients were homozygous for the F allele, 41.18% were heterozygous, and 11.76% were homozygous for the f allele. A considerable number of patients demonstrated impaired renal function with increased serum cystatin C levels (29.41%), glomerular dysfunction with proteinuria (68%), as well as significant tubulopathy with hypercalciuria (73.08%), and increased levels of urinary β2-microglobulin (29.41%). When patients were stratified according to Fok-I polymorphism, a significantly higher prevalence of abnormally increased serum levels of cystatin C was observed in patients being homozygous for the f allele (75%) compared with those being heterozygous (Ff) or homozygous for the F allele (14.29% and 31.25%, respectively, P = .02). Further studies are needed to confirm these preliminary results and elucidate the possible mechanisms involved.