VITAMIN-D-RECEPTOR (VDR) AND PARATHYROID-HORMONE MESSENGER-RIBONUCLEIC-ACID LEVELS CORRESPOND TO POLYMORPHIC VDR ALLELES IN HUMAN PARATHYROID TUMORS

Calcitriol, via its receptor (VDR) is a main regulator of PTH secretio n and parathyroid cell proliferation. Recently, marked overrepresentat ion of the polymorphic VDR alleles b, a, and T was found in patients w ith primary hyperparathyroidism (pHPT), which suggests pathogenic impo rtance in the disease. Using the ribonuclease protection assay, relati ve VDR and PTH messenger ribonucleic acid (mRNA) levels of parathyroid adenomas from 42 patients with sporadic pHPT were related to these VD R polymorphisms. The tumors of patients homozygous for the b, a, or T alleles demonstrated significantly lower VDR and higher PTH mRNA level s than those exhibiting the BE, AA, or tt genotypes (P < 0.0001-0.02), whereas heterozygotes had intermediate values. A similar discrepancy was found when comparing the baT and non-baT haplotypes (0.042 +/- 0.0 05 vs. 0.064 +/- 0.004 for VDR; 34.4 +/- 3.7 vs. 21.6 +/- 2.2 for PTH; both P < 0.005). The lower VDR mRNA levels associated with the b, a, and T alleles may affect the calcitriol-mediated control of parathyroi d function and thereby contribute to the development of sporadic pHPT.