Antilipolytic effect of calcimimetics depends on the allelic variant of calcium-sensing receptor gene polymorphism rs1042636 (Arg990Gly)
Author
dc.contributor.author
Reyes Jedlicki, Marcela
Author
dc.contributor.author
Rothe, Hansjörg M.
es_CL
Author
dc.contributor.author
Mattar, Pamela
es_CL
Author
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Shapiro, Warren B.
es_CL
Author
dc.contributor.author
Cifuentes, Mariana
es_CL
Admission date
dc.date.accessioned
2014-01-02T20:08:12Z
Available date
dc.date.available
2014-01-02T20:08:12Z
Publication date
dc.date.issued
2012
Cita de ítem
dc.identifier.citation
European Journal of Human Genetics (2012) 20, 480–482
en_US
Identifier
dc.identifier.other
doi:10.1038/ejhg.2011.221
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/124031
Abstract
dc.description.abstract
Calcium-sensing receptor polymorphism rs1042636 (Arg990Gly) affects the response to the calcimimetic cinacalcet, used to
treat hypercalcemia in secondary hyperparathyroidism (sHPT) or parathyroid carcinoma. Carriers of the Arg allelle, show less
parathyroid hormone secretion suppression in response to the drug. This effect was reproducible in transfected cultured human
embryonic kidney cells, supporting a causal relationship on the protein level. We previously established that cinacalcet has an
antilipolytic effect in isolated human adipocytes; however, there were a number of samples that did not respond to the
treatment. The present work aimed to investigate whether the variable antilipolytic response to cinacalcet in adipocytes was
consistent with the effect reported for the rs1042636 polymorphism. Lipolysis was assessed by measuring glycerol release
after exposure to cinacalcet (10 lM) or vehicle in adipocytes isolated from 38 donors. Responsiveness was defined as lipolysis
suppression (cinacalcet vs vehicle control) greater than 20%. Genotype analysis showed that 23 adipocyte donors were
homozygous for Arg at position 990, 14 heterozygous and 1 homozygous Gly–Gly. Among the Arg homozygotes, one was
responsive to cinacalcet, whereas five Gly carriers responded to the calcimimetic. In all, 83% of adipocytes showing response
to cinacalcet carried the glycine allele, whereas in 96% of Arg–Arg individuals adipocytes did not respond to the calcimimetic
(P¼0.027, Fisher’s exact test). Confirming sHPT observations, adipocytes from rs1042636 Gly-allele carriers show higher
sensitivity to the antilipolytic action of cinacalcet. The potential benefit of cinacalcet as a suppressor of basal lipolysis and free
fatty acid release in uremic patients needs to consider the rs1042636 single-nucleotide polymorphism.