Association of Klotho gene polymorphism (rs1207568) and serum miR-192 expression with secondary hyperparathyroidism in Egyptian hemodialysis patients

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Aly D.M.; Fteah A.M.; El-Shishtawy S.; Sherif N.

Journal: Egyptian Journal of Medical Human Genetics

Publisher: Springer Nature

Publication Date: 8 February 2026

Volume / Issue: Volume 27 / Issue 1

Article No.: 12

ISSN: 11108630

DOI: 10.1186/s43042-026-00844-6

Scopus: View on Scopus

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Aly D.M., Department of Clinical Chemistry, Theodor Bilharz Research Institute, Giza, Egypt; Fteah A.M., Department of Clinical Chemistry, Theodor Bilharz Research Institute, Giza, Egypt; El-Shishtawy S., Department of Nephrology, Theodor Bilharz Research Institute, Giza, Egypt Institute, Giza, Egypt; Sherif N., Department of Nephrology, Theodor Bilharz Research Institute, Giza, Egypt Institute, Giza, Egypt

Abstract

Background: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease–mineral and bone disorder (CKD-MBD) in patients receiving maintenance hemodialysis. Genetic and epigenetic regulators of mineral metabolism, including Klotho gene polymorphisms and microRNAs, have emerged as potential contributors to disease susceptibility; however, their clinical relevance remains incompletely defined. This study investigated the association of the Klotho rs1207568 polymorphism and serum microRNA-192 (miR-192) expression with SHPT in Egyptian hemodialysis patients. Methods: This case–control study included 200 maintenance hemodialysis patients (100 with SHPT and 100 without SHPT) and 100 healthy controls. SHPT was defined as intact parathyroid hormone (iPTH) > 65 pg/mL. Genotyping of Klotho rs1207568 was performed using TaqMan real-time PCR, and serum miR-192 expression was quantified by qRT-PCR. Clinical and biochemical parameters were compared across genotype groups. Multivariable logistic and linear regression analyses were conducted with adjustment for age, sex, dialysis duration, diabetes status, serum calcium, and phosphate. Results: The AA genotype and A allele of Klotho rs1207568 were significantly more frequent in hemodialysis patients with SHPT. In adjusted analyses, the A allele was independently associated with increased odds of SHPT (OR = 2.37,p < 0.001). Serum miR-192 expression was significantly downregulated in SHPT patients compared with non-SHPT patients and healthy controls (p < 0.001). Lower miR-192 expression remained independently associated with SHPT after multivariable adjustment (β = −2.786, p < 0.001). Receiver operating characteristic analysis demonstrated moderate diagnostic performance of miR-192 for SHPT (AUC = 0.751). Conclusion: Klotho rs1207568 polymorphism and reduced serum miR-192 expression are independently associated with SHPT in Egyptian maintenance hemodialysis patients. These findings suggest that genetic variation in Klotho and epigenetic regulation via miR-192 may contribute to disordered mineral metabolism in end-stage kidney disease. Further large-scale studies with comprehensive CKD-MBD phenotyping are warranted. © The Author(s) 2026.

Keywords

Haemodialysis-MBD; Klotho; miR-192; PCR; SNV; calcium ion; klotho protein; microRNA 192; parathyroid hormone; phosphate; adult; age; allele; Article; biochemical analysis; calcium blood level; case control study; clinical feature; controlled study; diabetes mellitus; disease association; DNA polymorphism; down regulation; Egyptian; epigenetics; female; gender; gene expression; genetic association; genetic variation; genotype; genotyping; hemodialysis patient; human; Klotho gene; linear regression analysis; major clinical study; male; middle aged; multivariate logistic regression analysis; parathyroid hormone blood level; phosphate blood level; real time polymerase chain reaction; receiver operating characteristic; reverse transcription polymerase chain reaction; secondary hyperparathyroidism; serum; treatment duration

Citation Information

Scopus Citations: 0

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