Association of Three HIF ‐1α Genotypes With Susceptibility and Severity of Chronic Kidney Disease

Abstract

Hypoxic signaling is a critical factor in the pathogenesis of Chronic Kidney Disease (CKD). Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that is highly expressed in the kidney and is associated with renal tubular hypoxic adaptation. Variation in the HIF-1α subunit gene has been associated with renal pathologies. This study investigated the association between three single-nucleotide polymorphisms (SNPs) in the HIF-1α gene: rs11549465 (P582S) in the Oxygen-Dependent Degradation Domain (ODDD), and two intronic SNPs, rs1957757, and rs1951795, with prevalence and severity of CKD. Primary genotypes were compared between 90 CKD patients (Stages II-V) and 48 healthy controls. Results revealed that the rs1951795 AA genotype was significantly more prevalent in the CKD group (30%) than in controls (5%) (p = 0.0017). Furthermore, specific genotypes correlated strongly with advanced disease stages: the P582S TT genotype was associated with an 18.07-fold increased adjusted odds of Stage IV CKD (p = 0.039), while the rs1957757 TT genotype carried an 11.16-fold increased odds of Stage V (p = 0.012). The rs1951795 AA genotype also showed an 8.33-fold increased odds for Stage V (p = 0.008). These findings suggest that variations in both the ODDD and intronic regions in the HIF-1α gene influence CKD susceptibility and progression. These SNPs may serve as important genetic markers for predicting the progression of CKD.