Possible Implication of Lecam-1 Gene P213s Polymorphism in the Risk for Advanced Stages of Diabetic Nephropathy in Patients with Type 1 Diabetes

Diabetic nephropathy has an unclarified pathogenesis, with multifactorial aetiology which includes metabolic and haemodynamic abnormalities, aberrant signaling of numerous cytokines or growth factors and genetic susceptibility. Inflammation and low birth weight seems to be predisposing factors for diabetic nephropathy. In both processes levels of L-selectin (CD62L) may play an important role. The genetic heritability of diabetic nephropathy and CD62L levels sustain the investigation of relationship between LECAM polymorphisms and the disease risk. The aim of the study was to investigate a possible relationship between Pro213Ser polymorphism in LECAM-1 gene and advanced stages of diabetic nephropathy in type 1 diabetes. We enrolled unrelated Caucasian patients with type 1 diabetes mellitus, fall into control group – diabetic patients with duration of disease over 20 years without microalbuminuria (n = 83) and nephropathy group – patients with overt nephropathy or end stage renal disease – ESRD (n = 121). Pro213Ser polymorphism genotyping was achieved using PCR-RFLP technique. Genotype spread analysis indicates that ProSer and SerSer are more frequent in the nephropathy group (ProSer = 41.95% and SerSer = 6.02 %), compared with the control group (ProSer = 20.53% and SerSer = 1.73%). The corrected OR's due to the small number of patients pointed the possibility that the 213Ser is the risk allele (ORSer = 1.634; p=0.04), and 213Pro is the protective one (ORPro = 0.602; p=0.04) regarding diabetic nephropathy. Thus our results suggest a possible association between the P213S polymorphism and advanced stages of diabetic nephropathy in type 1 diabetic patients. Additional researches are required in order to acknowledge the mentioned results and to clarify the mechanism by which this polymorphism intervenes in the disease pathogenesis.