Personalized medicine · 2008
CaSR polymorphism Arg990Gly and response to calcimimetic agents in end-stage kidney disease patients with secondary hyperparathyroidism and in cell culture.
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Rothe Hansjörg, Shapiro Warren, Sun Wei Y, Matalon Albert
Аннотация
AIMS: Calcimimetics are effective in reducing parathyroid hormone (PTH) levels in patients with secondary hyperparathyroidism, but variability in dose response has been noted. We examined SNP Arg990Gly of the calcium-sensing receptor as a possible cause.
MATERIALS & METHODS: We performed a dose-response study with cinacalcet on 23 hemodialysis patients (with PTH >300 pg/ml). Intact (i)PTH levels were measured at baseline and over time post-dose; 17 patients had iPTH measured at 24 h post-dose (60 mg). Arg990Gly status was established by sequencing a section from exon 7 of the CaSR gene.
RESULTS: Only 33% of patients homozygous for the arginine allele showed an iPTH suppression of at least 5% of baseline at 24 h, while 88% of patients with one or two glycine alleles achieved this target (p < 0.05).
CONCLUSION: We conclude that Arg990Gly influences the response to calcimimetics in patients with secondary hyperparathyroidism with an odds ratio of 2.6. This corresponds with in vitro data testing the effect of calcimimetic agent R-568 in HEK-293 cells transfected with the two alleles of Arg990Gly: HEK-293 cells expressing glycine-type CaSR were more sensitive to R-568 than arginine-type CaSR (p = 0.0001).
MATERIALS & METHODS: We performed a dose-response study with cinacalcet on 23 hemodialysis patients (with PTH >300 pg/ml). Intact (i)PTH levels were measured at baseline and over time post-dose; 17 patients had iPTH measured at 24 h post-dose (60 mg). Arg990Gly status was established by sequencing a section from exon 7 of the CaSR gene.
RESULTS: Only 33% of patients homozygous for the arginine allele showed an iPTH suppression of at least 5% of baseline at 24 h, while 88% of patients with one or two glycine alleles achieved this target (p < 0.05).
CONCLUSION: We conclude that Arg990Gly influences the response to calcimimetics in patients with secondary hyperparathyroidism with an odds ratio of 2.6. This corresponds with in vitro data testing the effect of calcimimetic agent R-568 in HEK-293 cells transfected with the two alleles of Arg990Gly: HEK-293 cells expressing glycine-type CaSR were more sensitive to R-568 than arginine-type CaSR (p = 0.0001).