Assessing the genetic contribution of certain GAS6/AXL variants to diabetic kidney disease susceptibility in Egyptian patients: a case–control observational study

Abstract Background Diabetic kidney disease (DKD) denotes the structural and functional alterations in renal tissues occurring as a diabetic complication. Growth arrest-specific 6 (GAS6) and its receptor AXL have been identified as biological markers linked to DKD. Single nucleotide polymorphisms (SNPs) serve as valuable markers for assessing polygenic diseases like DKD. This study investigated the association of GAS6 rs8191974, rs9577873, AXL rs2304232, and rs4802113 with DKD in Egyptians. Methods SNP selection was based on previous literature, and potential functional impact according to Ensembl Variant Effect Predictor. The SNPs were genotyped in 70 type 2 diabetic patients with normal kidney functions and diabetic duration > 5 years as the DM group, 70 type 2 diabetic patients showing microalbuminuria (30–300 mg/day) as the DKD group, and 60 apparently healthy controls, using TaqMan genotyping assays. Glycosylated hemoglobin, plasma creatinine and fasting plasma glucose levels were determined spectrophotometrically. Urinary albumin, plasma GAS6 and AXL levels were assayed using ELISA kits. Results Genotyping of the SNPs in cases and controls fitted the Hardy–Weinberg equilibrium ( p > 0.05). The genotypic frequencies as compared between cases and controls for rs8191974 ( p = 0.609, χ 2 = 2.703), rs9577873 ( p = 0.916, χ 2 = 4.611), rs2304232 ( p = 0.215, χ 2 = 5.799) and rs4802113 ( p = 0.742, χ 2 = 6.828) revealed no statistically significant differences. Genotypic variation in the analyzed SNPs within each group did not influence plasma GAS6 or AXL levels. No significant associations were noticed between studied parameters and SNP alleles. Conclusion No significant association was found between GAS6 rs8191974, GAS6 rs9577873, AXL rs2304232, or AXL rs4802113 and the development of type 2 diabetes or DKD in Egyptians. To date, this is the first genetic study assessing GAS6/AXL gene variants association with DKD in the Egyptian population.