VITAMIN-D-RECEPTOR GENOTYPES IN PRIMARY HYPERPARATHYROIDISM

Vitamin D and parathyroid hormone (PTH) constitute the main regulators of systemic calcium homeostasis. As well as its calcaemic effects, ac tive vitamin D-3 (1,25(OH)(2)D-3) has a direct regulatory role on para thyroid cells. Active vitamin D-3 acts via its receptor (VDR), and bin ding of the ligand-receptor complex to specific promotor regions of th e PTH gene inhibits transcription(1). Active vitamin D-3 constitutes a principal regulator of parathyroid cell growth(2,3), and polymorphism in the VDR gene has recently been related to bone mineral density and suggested as predisposing to osteoporosis(4). Impaired effects of act ive vitamin D-3 may contribute to the relatively enhanced secretion an d cell proliferation seen in hyperparathyroidism (HPT). Indeed, VDR dy sfunction, of essentially unknown character, has been demonstrated in the pathological parathyroid tissue of primary HPT as well as HPT seco ndary to uraemia(5,6). Consistent with the essential role of active vi tamin D-3 in parathyroid regulation, the VDR gene polymorphism was stu died in 90 postmenopausal women with primary hyperparathyroidism. The VDR genotype bb was found in 60.0% of HPT patients and in 33.3% of the postmenopausal female controls (P < 0.001). As the b allele has been linked to decreased transcriptional activity or messenger RNA stabilit y(4,7), reduced VDR expression may impede regulatory actions of vitami n D and may contribute to parathyroid tumorigenesis in these patients.