Fok-I gene polymorphism of vitamin D receptor in patients with beta-thalassemia major and its effect on vitamin D status

Most of the biological actions of vitamin D are mediated by an intracellular receptor (VDR) in which several single nucleotide gene polymorphisms have been identified. Vitamin D deficiency is increasingly identified among thalassemic patients and recent evidence links it with myocardial iron accumulation. The aim of this work was to assess the distribution of the Fok-I polymorphism of the VDR gene among Greek children and young adults with beta-thalassemia major and to investigate its association with 25(OH)D-3 and 1,25(OH)(2)D-3 serum levels. Sixty-nine thalassemic patients (35 females and 34 males), with a mean age of 23.05 +/- 6.07 years, participated in the study. Genotype frequencies of Fok-I were similar to those previously reported for other populations; 44.9% of the patients were homozygotes for F allele, 43.5% were heterozygotes and 11.6% were homozygotes for the f allele. Low levels of serum 25(OH)D-3 were recorded, as 41 patients (59.4%) were below the cut-off limit of 50 nmol/l that determines deficiency, whereas, levels of 1,25(OH)(2)D-3 showed wide variability ranging from deficiency (<= 50 pmol/l) in 34 patients (49.3%) to excess (>= 125 pmol/l) in 13 patients (18.8%). When stratifying patients according to serum 1,25(OH)(2) D-3 concentrations, a higher prevalence of the f allele was observed in the deficiency group (P=0.03). A comparison of the serum concentrations of the two vitamin D metabolites produced a trend towards a negative correlation (r=-0.204, P=0.09). Further studies are required to assess the genetic contribution to the regulation of vitamin D metabolites in the serum of patients with beta-thalassemia major.