Allelic loss at the vitamin D receptor ( VDR ) locus in parathyroid tissue from one patient affected by refractory uremic hyperparathyroidism

It has been established that secondary hyperparathyroidism (SHPT) represents a long-term complicance of chronic renal failure (CRF) associated to diffuse or nodular hyperplasia of parathyroid glands. The molecular mechanisms underlying both hyperactivity and proliferation rate of parathyroid cells in uremic patients have not yet been elucidated. A decreased sensitivity to vitamin D feedback is considered one of the causes accounting for parathyroid hyperplasia in CRF. Thus, we investigated the possible role that VDR gene may play in the development of parathyroid tumors in three female patients exhibiting refractory SHPT. We detected in one parathyroid nodular lesion from one patient a loss of heterozygosity within the VDR locus with acquisition of the haplotype previously described to segregate with lower bone mass values and lower intestinal calcium absorption efficiency in Italian postmenopausal women. These findings suggest that qualitative/ quantitative deficiency of VDR physiological activity may have a role in the pathogenesis of secondary hyperparathyroidism in uremic patients.