Vitamin D receptor gene polymorphism detected by digestion with Apa I influences the parathyroid response to extracellular calcium in Japanese chronic dialysis patients

Citation
K. Yokoyama et al., Vitamin D receptor gene polymorphism detected by digestion with Apa I influences the parathyroid response to extracellular calcium in Japanese chronic dialysis patients, NEPHRON, 89(3), 2001, pp. 315-320
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
NEPHRON
ISSN journal
0028-2766 → ACNP
Volume
89
Issue
3
Year of publication
2001
Pages
315 - 320
Database
ISI
SICI code
0028-2766(200111)89:3<315:VDRGPD>2.0.ZU;2-X
Abstract
Background. To play its physiological role, 1,25(OH)(2)D-3 must bind to a s pecific vitamin D receptor (VDR) in the nucleus. We have previously reporte d that VDR gene polymorphism influences the parathyroid function in patient s with end-stage renal disease (ESRD). In the present study, we have invest igated the relationship between the parathyroid responsiveness and VDR gene polymorphism, as detected by the Apa I restriction enzyme, by changing the concentration of Ca2+ in the dialysate. Methods: 58 Japanese ESRD patients undergoing renal replacement therapy in our institution were evaluated. Ge nomic DNA was extracted from peripheral leukocytes and digested at the intr on between exon 8 and exon 9 of the VDR gene using Apa I enzyme. Then allel es were classified into genotype A (undigested allele) and genotype a (dige sted allele). Extracellular ionized calcium ([Ca2+](e)), serum phosphate, a nd intact parathyroid hormone (PTH) were measured before and after each hem odialysis (HD) session with dialysates having different concentrations of C a2+ (1.5 or 1.25 mmol/l). The significance of differences in statistical an alyses was defined within confidence limits of 5.0%. Results: The AA, Aa, a nd aa genotypes were observed in 7/58 patients (12.1%), 23/58 patients (39. 6%), and 28/58 patients (48.3%), respectively. The PTH reduction after HD w ith the 1.5-mmol/l Ca dialysate did not differ significantly between group AA+Aa and group aa. On the other hand, the PTH increase was significantly h igher in group aa than in group AA+Aa after HD with the 1.25-mmol/l Ca dial ysate (p = 0.0107), despite a similar PTH level before HD. Similarly, the p ercent increase of PTH after HD with the 1.25-mmol/l Ca dialysate was signi ficantly higher (p = 0.0112) in group aa (50.2 +/- 9.4%) than in group AA+A a (19.7 +/- 7.2%). There were no significant differences between the two gr oups in [Ca2+](e) nor in serum phosphorus (Pi) before and after HD with eit her dialysate. Group AA+Aa and group aa did not show statistically signific ant differences in age, female/male ratio, ratio of diabetic nephropathy, o r dialysis period. Conclusions: The study results showed that the patients in group aa were more sensitive to changes in [Ca2+](e) than those in group AA+Aa. Moreover, they suggested that the VDR gene polymorphism may affect parathyroid responsiveness to changes in [Ca2+](e), which in turn may influ ence onset and progression of hyperparathyroid ism in ESRD patients. Copyri ght (C) 2001 S. Karger AG, Basel.