Vitamin D Receptor Polymorphisms in Hypocalcemic Vitamin D-Resistant Rickets Carriers

<i>Background/Aims:</i> Hypocalcemic vitamin D-resistant rickets (HVDRR) is a rare autosomal recessive disorder characterized by severe rickets, hypocalcemia, secondary hyperparathyroidism, elevated levels of 1,25-dihydroxyvitamin D<sub>3</sub> [1,25(OH)<sub>2</sub>D<sub>3</sub>], and occasionally, alopecia. In most cases, the disease is associated with mutations in the gene of the vitamin D receptor (VDR), the mediator of 1,25(OH)<sub>2</sub>D<sub>3</sub> action. The apparently healthy HVDRR heterozygotes express both normal and mutant VDR alleles, and they present higher levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> than their respective controls. Because VDR function, except for the disease-causative mutations, might be influenced by the presence of certain polymorphisms, we investigated the distribution of four common VDR polymorphisms –<i> Bsm</i>I, <i>Apa</i>I, <i>Taq</i>I and <i>Fok</i>I – in HVDRR carriers compared with their respective controls. <i>Methods:</i> Sixty-seven relatives of 2 HVDRR patients, all members of an extended Greek kindred, were included in the study. VDR allelic polymorphisms were assessed by restriction fragment length polymorphisms after specific polymerase chain reaction amplification. <i>Results:</i> The distribution of genotypic and allelic frequencies differed between HVDRR carriers and their respective controls regarding <i>Bsm</i>I and <i>Taq</i>I polymorphisms. The bb genotype and the T allele (presence of <i>Bsm</i>I and absence of <i>Taq</i>I polymorphisms) were less frequent in the HVDRR carrier group than in the control group in a statistically significant manner (p = 0.029 and p = 0.025, respectively). <i>Conclusions:</i> Our findings showed that the apparently healthy HVDRR carriers present a different distribution of <i>Bsm</i>I and <i>Taq</i>I VDR polymorphisms than their controls, suggesting that further investigation of the HVDRR carrier population may elucidate the implication of VDR alleles in VDR function and the vitamin D endocrine system.