Frequency of the calcium-sensing receptor variant A986S in patients with primary hyperparathyroidism

Objective: Recent studies have shown an influence of the calcium-sensing re ceptor variant A986S on the serum calcium concentration. suggesting that th is genetic variant could be a candidate for various bone and mineral disord ers. The intention of this study was therefore to investigate the frequency of the described calcium-sensing receptor variants A986S, R990G and Q1011E in patients with primary hyperparathyroidism to test the hypothesis as to whether these variants represent risk factors for the development of primar y hyperparathyroidism. Design: Fifty patients with primary hyperparathyroidism were included in th e study. One hundred and two healthy blood donors served as controls. Methods: Detection of the genetic variants A986S, R990G and Q1011E was done by direct sequencing of exon 7 of the calcium-sensing receptor in leucocyt e DNA. Results: The heterozygous variant A986S was found in 34% (17 of 50) of the healthy age- and sex-matched controls and 40% (20 of 50) of the patients wi th primary hyperparathyroidism. This difference was not statistically signi ficant (P=0.68). However, in male patients the heterozygous variant A986S w as found more frequently (67%, 6 of 9) than in male controls (20%, 2 of 10, P=0.07). The variants R990G and Q1011E were found less frequently (8-20%) in patients and controls without significant differences between the groups . Patients with the heterozygous variant Q1011E had significantly higher se rum calcium and parathyroid hormone levels than patients with the wild-type variant (P<0.01). There was no correlation of serum calcium (total and cor rected for albumin) with the calcium sensing receptor variant A986S in 102 healthy blood donors (P=0.45). Conclusions: The calcium-sensing receptor variants do not, therefore. seem to be major genetic determinants for the development of primary hyperparath yroidism. The variant A986S may possibly represent a risk factor for the de velopment of parathyroid neoplasia in men. Moreover, the presence of the ge notype Q1011E might influence the clinical course of the disease. The previ ously reported significant correlation of serum calcium levels with the gen etic variant A986S in healthy subjects could not be confirmed.