Common genetic variants in dyslipidemia, inflammation, and angiogenesis pathways associated with diabetic nephropathy in Tunisians.

INTRODUCTION: Dyslipidemia, inflammation and angiogenesis pathways contribute to the genetic susceptibility to diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM). This study investigated the association of common genetic variants; Apolipoprotein C1 (APOC1) rs4420638, C-C chemokine receptor type 5 (CCR5) rs1799987, C-X-C motif chemokine ligand 8 (CXCL8) rs4073, Matrix metallopeptidase 9 (MMP9) rs17576, Erythropoietin (EPO) rs1617640 and Vascular Endothelial Growth Factor A (VEGFA) (rs833061 and rs3025039) with DN susceptibility in Tunisian T2DM patients. MATERIALS AND METHODS: A total of 236 patients with T2DM were enrolled, including 47 with DN and 189 without diabetic nephropathy (WDN). Genotyping was performed using PCR-RFLP. Allelic combinations and statistical analyses were conducted using SNP Analyzer2.0 and SPSS20, respectively. RESULTS: All genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for potential confounding factors, the variant alleles of APOC1 rs4420638 (OR = 2.58, 95% CI: 1.01-6.63, p = 0.048) and CXCL8 rs4073 (OR = 2.66, 95% CI: 1.06-6.65, p = 0.037) were independently associated with an increased risk of DN. Combined allelic profiles were associated with higher estimated DN risk, with the APOC1-CXCL8 (GT) combination showing an OR of 3.43 (95% CI: 1.08-10.80, p = 0.036). CONCLUSION: APOC1 rs4420638 and CXCL8 rs4073 seem to be associated with DN risk in Tunisian T2DM patients both individually and within multilocus genetic profiles.