Genetic and inflammatory interplay between IL1B (-511C/T) polymorphism and diabetic nephropathy in type 2 diabetes

Inflammatory cytokines, particularly interleukin-1β (IL-1β), have a main role in diabetic nephropathy (DN) pathogenesis. Genetic variations within the IL1B promoter region may modulate cytokine expression and affect vulnerability to renal injury in type 2 diabetes mellitus (T2DM). We aimed to assess the correlation between the IL1B (-511C/T;rs16944) polymorphism, IL-1β serum levels, and renal function among Egyptian cases with T2DM.

This study was conducted on 150 subjects, who were divided into 50 T2DM cases with DN, 50 T2DM patients without DN, and 50 healthy control subjects recruited from Mansoura University Hospital. Genotyping of IL1B (-511C/T) was conducted by TaqMan real-time PCR, and serum IL-1β concentrations were quantified by ELISA. Clinical and biochemical parameters, including HbA1c, serum creatinine (Ser Cr), urinary albumin, and estimated glomerular filtration rate (eGFR), were analyzed.

The TT genotype (GT) was significantly more prevalent in DN cases (76%) than in diabetic (48%) and control (44%) groups (p = 0.008). TT carriers exhibited higher IL-1β levels (18.3 ± 13.5 pg/mL), HbA1c (7.6 ± 2.5%), serum creatinine (1.94 ± 1.3 mg/dL), and urinary albumin excretion, alongside lower eGFR (70.3 ± 22.9 mL/min/1.73m²) compared with CT/CC genotypes (p < 0.05).

The IL1B (-511T) allele is accompanied by enhanced IL-1β secration, poorer glycaemic control, and renal impairment in T2DM, suggesting a genetic predisposition to inflammation-driven DN. Screening for this variant may aid early risk stratification and personalized therapeutic targeting of IL-1β pathways in diabetic kidney disease (DKD).