a new potential mode of cardiorenal protection of klotho gene variability in type 1 diabetic adolescents

As the kl-vs haplotype alters secretion and activity of klotho and uric acid (ua) is associated with endothelial dysfunction and inflammation, their mutual links contribute to microalbuminuria (ma) in patients with type 1 diabetes (t1d). therefore, we hypothesize that kl-vs polymorphism could be associated with the prevalence of ma in t1d patients, and kl-vs polymorphism could modify physiological functions and pathogenic potential of ua. we have examined 350 patients with t1d. the analysis concerned kl-vs polymorphism along with the concentrations of serum inflammatory markers, indicators of renal function, blood pressure, and lipid profile. the incidence of kl-vs genotype was lower in a group with ma in comparison to patients without this condition. moreover, kl-vs carriers had improved indicators of renal function, lower concentrations of pro-inflammatory cytokines, and higher levels of anti-inflammatory markers. simultaneously, among kl-vs carriers serum ua was negatively correlated with hba1c, albumin excretion rate, acr, crp, tnf-α, total cholesterol, ldl-c and triglycerides, and positively correlated with hdl-c. moreover, among wild-type klotho carriers serum, ua was in positive correlation with creatinine, blood pressure, il-12 and mcp-1, and in negative correlation with il-10 and egfr. findings of our study suggest that the functional kl-vs polymorphism is independently associated with ma and the kl-vs genotype protects from the development of ma, and kl-vs polymorphism modify physiological functions and pathogenic potential of ua by altering the levels of hba1c, inflammatory biomarkers, indicators of renal function, blood pressure, and lipid profile. • we analyzed the kl-vs polymorphism and the ua serum level in patients with t1d. • the kl-vs polymorphism is independently associated with microalbuminuria. • the kl-vs alleles protect from the development of microalbuminuria. • kl-vs polymorphism modify physiological functions and pathogenic potential of uric acid.