Calcium-sensing receptor gene polymorphism affects the parathyroid response to moderate hypercalcemic suppression in patients with end-stage renal disease.
OBJECTIVE
The basic mechanism of secondary hyperparathyroidism is still unclear, but a change in Ca2+ sensing by parathyroid cells is possibly involved in this uremic complication. A rightward shift of the calcium set-point and an increase of the minimum secretion rate have been found in secondary hyperparathyroidism, indicating abnormal calcium sensing.


METHODS
We evaluated the effect of calcium sensing receptor (CaR) gene polymorphism (codon G990R) on the response of the parathyroid gland to moderate hypercalcemic suppression in 77 ESRD patients on regular hemodialysis (HD using 2.5 mEq/l Ca2+ dialysate). All patients underwent an HD session with 3.0 mEq/l Ca2+ dialysate to suppress parathyroid hormone (PTH). Then we investigated the effect of CaR gene polymorphism on the parathyroid response to hypercalcemic stimulation.


RESULTS
Patients were divided into 3 groups on the basis of genotype (GG = 33 patients (42.9%), GR = 39 patients (50.6%), RR = 5 patients (6.5%)). Baseline intact PTH levels in patients without the R allele were not significantly different from those in patients with the R allele (GG group, 181.4 +/- 31.1 pg/ml vs. GR and RR groups, 230 +/- 51.2 pg/ml: mean +/- SEM). The significant effect of moderate hypercalcemic suppression on the intact PTH level was observed in the GG group (p < 0.01) but not in the GR and RR groups, despite the identical increase in Ca2+.


CONCLUSIONS
Our results suggest that CaR gene polymorphism (codon G990R) influences the responsiveness of the parathyroid gland to changes of extracellular Ca2+ in ESRD patients. The glands of patients with the GG genotype of the CaR gene may be more sensitive to extracellular Ca2+ changes.
Yokoyama
K
K
The Division of Nephrology and Hypertension, Jikei University School of Medicine, Tokyo, Japan. keitaro@mrj.biglobe.ne.jp
Shigematsu
T
T
Tsukada
T
T
Hara
S
S
Yamada
A
A
Kawaguchi
Y
Y
Hosoya
T
T
D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D015312:Hemodialysis Solutions; D006801:Humans; D006934:Hypercalcemia / Q000150:complications / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D011110:Polymorphism, Genetic; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*; D006435:Renal Dialysis
D015312:Hemodialysis Solutions; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D002118:Calcium