Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis.
Adult
Aged
Calcimimetic Agents
/ therapeutic use
Chronic Kidney Disease-Mineral and Bone Disorder
/ complications
Cinacalcet
/ therapeutic use
Death, Sudden, Cardiac
/ epidemiology
Female
Fibroblast Growth Factor-23
Fibroblast Growth Factors
/ genetics
Genetic Predisposition to Disease
Glucuronidase
/ genetics
Heart Failure
/ genetics
Humans
Hyperparathyroidism, Secondary
/ etiology
Kaplan-Meier Estimate
Klotho Proteins
Male
Middle Aged
Multicenter Studies as Topic
Polymorphism, Single Nucleotide
Randomized Controlled Trials as Topic
Receptor, Fibroblast Growth Factor, Type 4
/ genetics
Renal Dialysis
Cardiovascular disease
Chronic kidney disease-mineral bone disorder
Dialysis
Fibroblast growth factor-23
Mortality
Journal
American journal of nephrology
ISSN: 1421-9670
Titre abrégé: Am J Nephrol
Pays: Switzerland
ID NLM: 8109361
Informations de publication
Date de publication:
2019
2019
Historique:
received:
12
09
2018
accepted:
04
12
2018
pubmed:
23
1
2019
medline:
3
4
2020
entrez:
23
1
2019
Statut:
ppublish
Résumé
Elevated serum concentrations of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality in patients with chronic kidney disease and those undergoing dialysis. We tested the hypotheses that polymorphisms in FGF23, its co-receptor alpha-klotho (KL), and/or FGF23 receptors (FGFR) are associated with cardiovascular events and/or mortality. We used 1,494 DNA samples collected at baseline from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial, in which patients were randomized to the calcimimetic cinacalcet or placebo for the treatment of secondary hyperparathyroidism. We analyzed European and African Ancestry samples separately and then combined summary statistics to perform a meta-analysis. We evaluated single-nucleotide polymorphisms (SNPs) in FGF23, KL, and FGFR4 as the key exposures of interest in proportional hazards (Cox) regression models using adjudicated endpoints (all-cause and cardiovascular mortality, sudden cardiac death, and heart failure [HF]) as the outcomes of interest. rs11063112 in FGF23 was associated with cardiovascular mortality (risk allele = A, hazard ratio [HR] 1.32, meta-p value = 0.004) and HF (HR 1.40, meta-p value = 0.007). No statistically significant associations were observed between FGF23 rs13312789 and SNPs in FGFR4 or KL genes and the outcomes of interest. rs11063112 was associated with HF and cardiovascular mortality in patients receiving dialysis with moderate to severe secondary hyperparathyroidism.
Sections du résumé
BACKGROUND
Elevated serum concentrations of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality in patients with chronic kidney disease and those undergoing dialysis.
OBJECTIVES
We tested the hypotheses that polymorphisms in FGF23, its co-receptor alpha-klotho (KL), and/or FGF23 receptors (FGFR) are associated with cardiovascular events and/or mortality.
METHODS
We used 1,494 DNA samples collected at baseline from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial, in which patients were randomized to the calcimimetic cinacalcet or placebo for the treatment of secondary hyperparathyroidism. We analyzed European and African Ancestry samples separately and then combined summary statistics to perform a meta-analysis. We evaluated single-nucleotide polymorphisms (SNPs) in FGF23, KL, and FGFR4 as the key exposures of interest in proportional hazards (Cox) regression models using adjudicated endpoints (all-cause and cardiovascular mortality, sudden cardiac death, and heart failure [HF]) as the outcomes of interest.
RESULTS
rs11063112 in FGF23 was associated with cardiovascular mortality (risk allele = A, hazard ratio [HR] 1.32, meta-p value = 0.004) and HF (HR 1.40, meta-p value = 0.007). No statistically significant associations were observed between FGF23 rs13312789 and SNPs in FGFR4 or KL genes and the outcomes of interest.
CONCLUSIONS
rs11063112 was associated with HF and cardiovascular mortality in patients receiving dialysis with moderate to severe secondary hyperparathyroidism.
Identifiants
pubmed: 30669147
pii: 000496060
doi: 10.1159/000496060
pmc: PMC6473180
mid: NIHMS1005998
doi:
Substances chimiques
Calcimimetic Agents
0
FGF23 protein, human
0
Fibroblast Growth Factors
62031-54-3
Fibroblast Growth Factor-23
7Q7P4S7RRE
FGFR4 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 4
EC 2.7.10.1
Glucuronidase
EC 3.2.1.31
Klotho Proteins
EC 3.2.1.31
Cinacalcet
UAZ6V7728S
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
125-132Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK100306
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002529
Pays : United States
Informations de copyright
© 2019 S. Karger AG, Basel.
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