Fibroblast growth factor-23 rs7955866 polymorphism and risk of chronic kidney disease

Abstract

BackgroundA missense gain-of-function fibroblast growth factor-23 (FGF23) gene single nucleotide polymorphism (SNP) (rs7955866) has been associated with FGF23 hypersecretion, phosphaturia, and bone disease. Excess circulating FGF23 was linked with atherosclerosis, hypertension, initiation, and progression of chronic kidney disease (CKD).MethodsThe study included 72 CKD stage 2/3 Egyptian patients (27–71 years old, 37 females) and 26 healthy controls matching in age and sex. Repeated measures of blood pressure were used to quantify hypertension on a semiquantitative scale (grades 0 to 5). Fasting serum urea, creatinine, uric acid, total proteins, albumin, calcium, phosphorus, vitamin D3, intact parathyroid hormone (iPTH), and intact FGF23 (iFGF23) were measured. DNA extracted from peripheral blood leucocytes was used for genotyping of FGF23 rs7955866 SNP using the TaqMan SNP genotyping allelic discrimination method.ResultsMajor causes of CKD were hypertension, diabetic kidney disease, and CKD of unknown etiology. There was no significant difference in minor allele (A) frequency between the studied groups (0.333 in GI and 0.308 in GII). Median (IQR) serum iFGF23 was significantly higher in GI [729.2 (531.9–972.3)] than in GII [126.1 (88.5–152.4)] pg/mL, P < 0.001. Within GI, the minor allele (A) frequency load, coded for codominant inheritance, had a significant positive correlation with both hypertension grade (r = 0.385, P = 0.001) and serum iFGF23 (r = 0.259, P = 0.028). Hypertension grade had a significant positive correlation with serum phosphorus and iFGF23.ConclusionsFor the first time in an Egyptian cohort, we report a relatively high frequency of the rs7955866 SNP. It may remain dormant or become upregulated in response to some environmental triggers, notably dietary phosphorus excess, leading to increased circulating iFGF23 with ensuing hypertension and/or renal impairment. Subjects with this SNP, particularly in the homozygous form, are at increased risk for CKD of presumably “unknown” etiology, with a tendency for early onset hypertension and increased circulating iFGF23 out of proportion with the degree of renal impairment. Large-scale population studies are needed to confirm these findings and explore the role of blockers of the renin–angiotensin–aldosterone system and sodium chloride cotransporters in mitigating hypertension associated with FGF23 excess.