Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis

Autor: Sharon M. Moe, Howard J. Edenberg, Leah Wetherill, Tatiana Foroud, Tae Hwi Schwantes-An, Margaret R. Stedman, Matteo Vatta, Sai Liu, Brian S. Decker, Glenn M. Chertow
Rok vydání: 2019
Předmět:
Adult
Male
Fibroblast growth factor 23
medicine.medical_specialty
Cinacalcet
Calcimimetic
medicine.medical_treatment
030232 urology & nephrology
Kaplan-Meier Estimate
Calcimimetic Agents
030204 cardiovascular system & hematology
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
0302 clinical medicine
Renal Dialysis
Internal medicine
medicine
Humans
Multicenter Studies as Topic
Genetic Predisposition to Disease
Receptor
Fibroblast Growth Factor
Type 4
Klotho Proteins
Dialysis
Aged
Glucuronidase
Randomized Controlled Trials as Topic
Chronic Kidney Disease-Mineral and Bone Disorder
Heart Failure
business.industry
Hazard ratio
Middle Aged
medicine.disease
Fibroblast Growth Factors
Fibroblast Growth Factor-23
Death
Sudden
Cardiac
Nephrology
Female
Hyperparathyroidism
Secondary
Secondary hyperparathyroidism
Hemodialysis
business
medicine.drug
Kidney disease
Zdroj: American Journal of Nephrology. 49:125-132
ISSN: 1421-9670
0250-8095
DOI: 10.1159/000496060
Popis: 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.
Databáze: OpenAIRE
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