Hypomethylation of the PTH gene due to high dietary phosphorus: A possible aggravating of severe secondary hyperparathyroidism in chronic renal failure

G. Bedia Díaz, N. Carrillo López, G. Solache Berrocal, A. Dusso, I. Rodríguez, Manuel Naves Díaz, J. B. Cannata Andía, P. Román García

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Hyperphosphataemia aggravates both parathyroid hyperplasia and PTH secretion in patients with chronic kidney disease (CKD). Hyperplasia is associated with decreases in calcium receptor expression (CaSR), vitamin D (VDR) and α-Klotho, inducing resistance of the parathyroid gland to respond both to treatment and to increases in FGF23. This study examined the possible epigenetic contributions of raised phosphorus to aggravate secondary hyperparathyroidism (SHPT) in patients with (CRD). Material and methods: The degree of methylation was compared by pyrosequencing of bisulfite in CpGrich sequences of the promoters in the CaSR, VDR, PTH and α-Klotho genes in parathyroid gland DNA from uremic rats fed a normal and high phosphorus diet. Results: The diet rich in phosphorus increased PTH expression and caused a marked reduction in the degree of methylation in the promoter of the PTH gene. In contrast, the promoter regions of the CaSR, VDR and α-Klotho genes did not show significant differences in the percentage of methylation between the two groups of rats. Thus, it was not the determining mechanism for the decrease of the expression of these genes observed in the SHPT. Conclusions: The epigenetic alterations induced by the phosphorus rich diet in SHPT, particularly the PTH gene hypomethylation, could contribute to the increases that occur in the synthesis and secretion of this hormone. The identification of the mechanisms involved would allow better treatments for SHPT to be designed in the early stages of CKD.

Original languageEnglish
Pages (from-to)114-120
Number of pages7
JournalRevista de Osteoporosis y Metabolismo Mineral
Volume9
Issue number4
DOIs
StatePublished - Dec 1 2017

Keywords

  • Chronic kidney disease
  • DNA methylation
  • Hiperphosphataemia
  • PTH
  • Parathyroid glands

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