KL rs9536314 variant
influencing mineral homeostasis and oxidative stress in diabetic CKD
Alfayadh Karrar, Dehghan Gholamreza, Khosroshahi Hamid Tayebi and Haghi Mehdi
Res. J. Biotech.; Vol. 21(2); 126-136;
doi: https://doi.org/10.25303/212rjbt1260136; (2026)
Abstract
Chronic kidney disease (CKD), often accompanied by mineral and bone disorders, is
worsened by diabetes. The Klotho-Fibroblast growth factor 23 (KL-FGF23) axis regulates
calcium and phosphorus balance and is linked to CKD progression. This study investigated
the rs9536314 KL gene polymorphism, serum KL and FGF23 levels, oxidative stress
and bone markers in pre-dialysis diabetic CKD patients. A total of 100 subjects,
comprising of 50 pre-dialysis diabetic patients and 50 healthy people, were enrolled
in the present cross-sectional study. Patients showed significantly reduced serum
KL (2.55±0.77 ng/mL vs. 4.51±0.65 ng/mL, P < 0.001) and elevated FGF23 (84.96±9.62
ng/mL vs. 22.83±6.74 ng/mL, P < 0.001) compared to the control group. In addition,
patients exhibited higher parathyroid hormone and phosphorus levels, indicating
disturbed mineral homeostasis. Oxidative stress markers, including malondialdehyde
and pro-oxidant/antioxidant balance, were significantly elevated, whereas glutathione
peroxidase activity was reduced in pre-dialysis patients, depicting a pronounced
oxidative stress state.
Genetic analysis of the rs9536314 KL polymorphism revealed no significant differences
in genotype or allele frequencies between groups (TT: OR = 0.77, 95% CI: 0.33–1.75;
TG: OR = 1.40, 95% CI: 0.63–3.11; GG: OR = 0.65, 95% CI: 0.10–4.08; allele G: OR
= 0.99, 95% CI: 0.55–1.78; all P > 0.4), indicating that this polymorphism may not
directly contribute to diabetic pathogenesis in pre-dialysis patients. Overall,
while the KL rs9536314 polymorphism did not show a significant association with
disease risk, the pronounced alterations in Klotho, FGF23 and oxidative stress markers
reveal their potential role as biomarkers and therapeutic targets in CKD progression.
