Association of klotho gene polymorphism and the regulation of calcium-phosphate metabolism disorders in patients with end-stage renal disease

Nephrology (Carlton). 2019 Oct;24(10):1001-1008. doi: 10.1111/nep.13547. Epub 2019 May 2.

Abstract

Background: Klotho G-395-A gene polymorphism is associated with several diseases; however, its association with calcium-phosphate metabolism disorders in end-stage renal disease (ESRD) is unknown.

Methods: A total of 137 patients with ESRD and 80 healthy adults (control) were enrolled in the study. Patients with ESRD were divided into three subgroups: haemodialysis (A1, n = 52), peritoneal dialysis (A2, n = 30), and non-dialysis (A3, n = 55). The klotho G-395-A genotype was detected by TaqMan PCR assay, and ELISA was used to detect the soluble klotho protein (sKL) and fibroblast growth factor (FGF23). Intact parathyroid hormone (iPTH) and other related clinical biochemical parameters were also analyzed for all subjects.

Results: (i) Three genotypes (GG, GA and AA) of KL G-395A were detected, and a significant difference between the ESRD and control groups was observed, (ii) sKL was inversely associated with FGF23 in each subgroup and phosphate and positively associated with calcium in A1 and A3. FGF23 was positively associated with phosphate and inversely associated with calcium in each subgroup, (iii) a statistical difference in levels of sKL and FGF23 was observed between GG and AA, as well as between GA and AA. The expression of sKL was lowest and the level of FGF23 was highest in AA and (iv). GA + AA genotypes and FGF23 were risk factors and sKL might be protective factor of calcium-phosphate metabolism disorders.

Conclusion: Soluble klotho protein and FGF23 were associated with the regulation of calcium and phosphate metabolism, and the A allele of the G-395A klotho gene polymorphism could be a risk factor on calcium-phosphate metabolism disorders in patients with ESRD.

Keywords: FGF23; calcium-phosphate metabolism; end-stage renal disease; klotho polymorphism; klotho protein.

MeSH terms

  • Adult
  • Calcium / metabolism*
  • Calcium Metabolism Disorders* / diagnosis
  • Calcium Metabolism Disorders* / genetics
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Glucuronidase / blood
  • Glucuronidase / genetics*
  • Humans
  • Kidney Failure, Chronic* / genetics
  • Kidney Failure, Chronic* / metabolism
  • Kidney Failure, Chronic* / therapy
  • Klotho Proteins
  • Male
  • Phosphates / metabolism*
  • Phosphorus Metabolism Disorders* / diagnosis
  • Phosphorus Metabolism Disorders* / genetics
  • Polymorphism, Genetic
  • Renal Replacement Therapy / methods

Substances

  • FGF23 protein, human
  • Phosphates
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Glucuronidase
  • Klotho Proteins
  • Calcium