Association of IL-8 rs4073 −251T>A gene polymorphism with diabetic nephropathy in patients with type 2 diabetes mellitus

BACKGROUND: Diabetic nephropathy (DN) is one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and a leading cause of chronic kidney disease worldwide. Inflammatory pathways play a key role in the pathogenesis and progression of DN. Interleukin-8 (IL-8), a pro-inflammatory cytokine involved in leukocyte recruitment and activation, has been associated with renal inflammation and albuminuria. However, the contribution of IL-8 gene polymorphisms to susceptibility and progression of DN remains unclear. MATERIALS AND METHODS: This cross-sectional case-control study included 138 patients with T2DM and 138 age- and sex-matched healthy controls. Diabetic patients were stratified according to the presence of DN based on urinary albumin excretion and diabetic retinopathy. Genomic DNA was isolated from peripheral blood samples, and the IL-8 rs4073 -251T>A polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Genotype and allele frequencies were compared between groups, and clinical and laboratory parameters were evaluated according to genotype status. RESULTS: Genotype distributions of the IL-8 rs4073 -251T>A polymorphism were similar between T2DM patients and controls, suggesting no association with the development of T2DM. Among diabetic patients, however, the AA genotype was detected only in individuals without nephropathy and was absent in both latent and overt DN groups. Patients lacking the AA genotype demonstrated higher urinary albumin excretion and a greater frequency of nephropathy progression. DN patients also exhibited longer diabetes duration, poorer glycemic control, impaired renal function, and elevated inflammatory markers compared with patients without nephropathy. Additionally, an inverse relationship between the presence of the A allele and leukocyte and neutrophil counts was observed. CONCLUSION: The IL-8 rs4073 -251T>A polymorphism does not appear to influence susceptibility to T2DM; however, the presence of the A allele may exert a protective effect against the development of diabetic nephropathy. This protective effect may be mediated through modulation of inflammatory pathways, as suggested by the inverse association between the A allele and inflammatory cell counts. Larger multicenter studies are required to confirm these findings.