Polyxeni Nicolaidou a , Anna Papadopoulou a , Y.G. Matsinos b , Helen Georgouli c , Andreas Fretzayas a , Anastasios Papadimitriou a , Kostantinos Priftis d , Konstantinos Douros a , George P. Chrousos e
13 November 2006
Background/Aims: 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 – BsmI, ApaI, TaqI and FokI – in HVDRR carriers compared with their respective controls. Methods: 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. Results: The distribution of genotypic and allelic frequencies differed between HVDRR carriers and their respective controls regarding BsmI and TaqI polymorphisms. The bb genotype and the T allele (presence of BsmI and absence of TaqI 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). Conclusions: Our findings showed that the apparently healthy HVDRR carriers present a different distribution of BsmI and TaqI 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.