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, active vitamin D-3 (1,25(OH)(2)D-3) has a direct regulatory role on parathyroid cells. Active vitamin D-3 acts via its receptor (VDR), and binding of the ligand-receptor complex to specific promotor regions of the 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 active vitamin D-3 may contribute to the relatively enhanced secretion and cell proliferation seen in hyperparathyroidism (HPT). Indeed, VDR dysfunction, of essentially unknown character, has been demonstrated in the pathological parathyroid tissue of primary HPT as well as HPT secondary to uraemia(5,6). Consistent with the essential role of active vitamin D-3 in parathyroid regulation, the VDR gene polymorphism was studied 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 stability(4,7), reduced VDR expression may impede regulatory actions of vitamin D and may contribute to parathyroid tumorigenesis in these patients.