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

Abstract

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.