Clinical, Biochemical, and Genetic Study of Patients with Hypertension Associated Kidney Disease

Abstract

Background: Hypertension (HTN) is the second leading cause of kidney failure, due to blood pressure (BP) rises and cause deterioration in kidney function. The biochemical and genetic mechanisms of HTN associated kidney diseases (HAKD) are still unclear.Objectives: To asses circulating levels of fibroblast growth factor 23 (FGF23), αklotho and mircoRNA-126 (mir-126) in patients with HAKD, to evaluate the genetic profile of klotho G-395A (rs1207568), C1818T (rs564481), and wnt signaling pathway AXIN-1 C>T (rs9921222) single nucleotide polymorphisms (SNPs).Patients and Methods: This cross-sectional case-control study included 50 patients have HAKD, and 50 healthy controls. Plasma concentrations of α klotho and FGF23 were assessed using ELISA assay kits, whereas mir-126 expression levels were quantified using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Genetic analysis of rs1207568, rs564481 and rs9921222 SNPs were performed using conventional PCR techniques.Results: The median FGF23 level in HAKD patients was significantly higher compared to controls, while the median αKlotho and mir-126 expression levels were much lower in HAKD patients compared to controls (P <0.01 for all). The genotyping of klotho rs1207568 showed significantly higher frequency of GG genotype in HAKD patients compared to the control group (P= 0.015), while regarding klotho rs564481, all participants have CT genotype. Wnt signaling pathway rs9921222 SNP showed a significant higher frequency of mutant homozygous TT genotype and mutant T allele in the HAKD group compared to controls, P =0.002, and 0.004 respectively). OR (95% CI) = 0.429 (0.24-0.766) for mutant T allele.Conclusion: Up regulation of FGF23 and down regulation of αKlotho and mir-126 expressions may have role in HAKD. GG genotype of Klotho rs1207568 SNP, TT genotype of wnt signaling pathway rs9921222 SNP and its mutant T allele were found to be a genetic risk factors in development of HAKD.