A new potential mode of cardiorenal protection of KLOTHO gene variability in type 1 diabetic adolescents

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ORIGINAL ARTICLE

A new potential mode of cardiorenal protection of KLOTHO gene variability in type 1 diabetic adolescents Bartosz Słomiński 1 & Monika Ryba-Stanisławowska 1 & Maria Skrzypkowska 1 & Magdalena Gabig-Cimińska 2,3 & Małgorzata Myśliwiec 4 Received: 24 October 2019 / Revised: 21 April 2020 / Accepted: 28 April 2020 # The Author(s) 2020

Abstract 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 may 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 may 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. Key messages • 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 may modify physiological functions and pathogenic potential of uric acid. Keywords Type 1 diabetes . KL-VS polymorphism . Uric acid . Microalbuminuria

* Bartosz Słomiński [email protected] 1

Department of Medical Immunology, Faculty of Medicine, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland

2

Department of Medical Biology and Genetics, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland

3

Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Laboratory of Molecular Biology, Kładki 24, 80-822 Gdańsk, Poland

4

Chair and Clinics of Paediatrics, Diabetology and Endocrinology, Faculty of Medicine, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland

Introduction Microalbuminuria (MA