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Vitamin D receptor genotypes in primary hyperparathyroidism

Abstract

Vitamin D and parathyroid hormone (PTH) constitute the main regulators of systemic calcium homeostasis. As well as its calcaemic effects, active vitamin D3(1,25(OH)2D3) has a direct regulatory role on parathyroid cells. Active vitamin D3 acts via its receptor (VDR), and binding of the ligand-receptor complex to specific promotor regions of the PTH gene inhibits transcription1. Active vitamin D3 constitutes a principal regulator of parathyroid cell growth2,3, and polymorphism in the VDR gene has recently been related to bone mineral density and suggested as predisposing to osteoporosis4. Impaired effects of active vitamin D3 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 uraemia5,6. Consistent with the essential role of active vitamin D3 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 stability4,7, reduced VDR expression may impede regulatory actions of vitamin D and may contribute to parathyroid tumorigenesis in these patients.

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Correspondence to Tobias Carling.

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Carling, T., Kindmark, A., Hellman, P. et al. Vitamin D receptor genotypes in primary hyperparathyroidism. Nat Med 1, 1309–1311 (1995). https://doi.org/10.1038/nm1295-1309

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