TaqI Polymorphism of Vitamin D Receptor Gene as a Potential Marker for Bone Complications in Transfusion Dependent Thalassemia Patients: Management Implications

Objective: Early detection of osteoporosis maybe possible by studying genetic factors which may include genetic differences in bone metabolism. These are imperative in the pathogenesis of thalassemia-induced osteoporosis which however the mechanism remains unclear. Till date this TaqI polymorphism of vitamin D receptor (VDR) gene is not widely studied in thalassemia that might have association with bone complications. This study was done to observe the frequency of TaqI SNPs in the VDR gene among transfusion dependent thalassemia patients.  Method: Fifty transfusion dependent thalassemia patients were recruited in this study and DNA was extracted using QIAamp Blood Maxi Kit. Subsequently, genomic DNA was used for the genotyping using RFLP-PCR method. Polymorphism at rs731236 (c.1056T>C) was detected by the TaqI restriction enzyme where lack of digestion indicates the presence of wild type T allele representing TT genotype at the locus while the cleavage indicates the presence of mutant C allele with genotypes either CT or CC. Allele and genotype frequencies were estimated by gene counting and tested for Hardy-Weinberg equilibrium.  Result: Out of 50 samples analyzed for TaqI polymorphism, the prevalence of TaqI VDR allele frequency ‘C’ found in our Malaysian transfusion dependent thalassemia patients was 16% (TT=68% and TC=32%).  Conclusion: Further prospective studies on a wider scale are required to fully clarify the precise environmental and genetic mechanisms underlying bone metabolism derangement in thalassemia children. This preliminary report showed 16% TaqI polymorphism carrier, hence its contribution to the thalassemia-induced osteoporosis should be explored. Please download the full paper by clicking on the PDF file below...