Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy

Diabetic nephropathy (DN) has become the major cause of end-stage kidney disease and is associated to an extremely high cardiovascular (CV) risk. We screened 318 DN patients for 23 SNPs in four glucose transporters (<i>SLC2A1</i>, <i>SLC2A2</i>, <i>SLC5A1</i> and <i>SLC5A2</i>) and in <i>KCNJ11</i> and <i>ABCC8</i>, which participate in insulin secretion. Regression models were utilised to identify associations with renal parameters, atherosclerosis measurements and CV events. In addition, 506 individuals with normal renal function were also genotyped as a control group. In the patient’s cohort, common carotid intima media thickness values were higher in carriers of <i>ABCC8</i> rs3758953 and rs2188966 vs. non-carriers [0.78(0.25) vs. 0.72(0.22) mm, <i>p</i> &lt; 0.05 and 0.79(0.26) vs. 0.72(0.22) mm, <i>p</i> &lt; 0.05], respectively. Furthermore, <i>ABCC8</i> rs1799859 was linked to presence of plaque in these patients [1.89(1.03-3.46), <i>p</i> &lt; 0.05]. Two variants, <i>SLC2A2</i> rs8192675 and <i>SLC5A2</i> rs9924771, were associated with better [OR = 0.49 (0.30-0.81), <i>p</i> &lt; 0.01] and worse [OR = 1.92 (1.15-3.21), <i>p</i> &lt; 0.05] CV event-free survival, respectively. With regard to renal variables, rs841848 and rs710218 in <i>SLC2A1</i>, as well as rs3813008 in <i>SLC5A2</i>, significantly altered estimated glomerular filtration rate values [carriers vs. non-carriers: 30.41(22.57) vs. 28.25(20.10), <i>p</i> &lt; 0.05; 28.95(21.11) vs. 29.52(21.66), <i>p</i> &lt; 0.05 and 32.03(18.06) vs. 28.14(23.06) ml/min/1.73 m², <i>p</i> &lt; 0.05]. In addition, <i>ABCC8</i> rs3758947 was associated with higher albumin-to-creatinine ratios [193.5(1139.91) vs. 160(652.90) mg/g, <i>p</i> &lt; 0.05]. The epistasis analysis of SNP-pairs interactions showed that <i>ABCC8</i> rs3758947 interacted with several SNPs in <i>SLC2A2</i> to significantly affect CV events (<i>p</i> &lt; 0.01). No SNPs were associated with DN risk. Polymorphisms in genes determining glucose homeostasis may play a relevant role in renal parameters and CV-related outcomes of DN patients.