Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Am J Nephrol. 2019;49(2):125-132. doi: 10.1159/000496060. Epub 2019 Jan 22.
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.
成纤维细胞生长因子 23（FGF23）的血清浓度升高与慢性肾脏病患者和透析患者的心血管死亡率相关。
我们检验了以下假设，即 FGF23、其共同受体 α-klotho（KL）和/或 FGF23 受体（FGFR）的多态性与心血管事件和/或死亡率相关。
我们使用了来自评估盐酸西那卡塞治疗降低心血管事件试验（Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial）的基线时采集的 1494 份 DNA 样本，该试验中患者被随机分配至钙敏感受体激动剂西那卡塞或安慰剂治疗继发性甲状旁腺功能亢进症。我们分别分析了欧洲和非洲血统的样本，然后合并汇总统计数据进行荟萃分析。我们评估了 FGF23、KL 和 FGFR4 中的单核苷酸多态性（SNP）作为主要暴露因素，使用调整后的终点（全因和心血管死亡率、心脏性猝死和心力衰竭[HF]）作为感兴趣的结局，在比例风险（Cox）回归模型中进行分析。
FGF23 中的 rs11063112 与心血管死亡率（风险等位基因=A，风险比[HR]1.32，meta-p 值=0.004）和 HF（HR1.40，meta-p 值=0.007）相关。在 FGFR4 或 KL 基因中 FGF23 rs13312789 与感兴趣的结局之间未观察到统计学显著关联。
在接受中度至重度继发性甲状旁腺功能亢进症透析治疗的患者中，rs11063112 与 HF 和心血管死亡率相关。
