Bartosz Słomiński1, Monika Ryba-Stanisławowska2, Maria Skrzypkowska2, Jolanta Myśliwska2, Małgorzata Myśliwiec3. 1. Department of Immunology, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland. Electronic address: bartosz@gumed.edu.pl. 2. Department of Immunology, Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland. 3. Chair & Clinics of Paediatrics, Diabetology and Endocrinology, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland.
Abstract
BACKGROUND AND AIMS: KLOTHO is an anti-ageing circulating hormone involved in insulin signaling, inflammation and vascular homeostasis through its protective effects on the endothelium and antioxidant actions. The common functional "KL-VS" variant of the KLOTHO gene is reproducibly associated with longevity in humans. Large number of studies have evaluated close relationship between KLOTHO protein and diabetes but the association between KL-VS variant and retinopathy in type 1 diabetes mellitus (T1D) is unknown. Therefore, in the present study we examined the association between the KL-VS polymorphism and the risk of diabetic retinopathy (DR) in patients with T1D. METHODS: We examined 400 patients with T1D and 350 healthy age-matched controls. The analysis concerned KL-VS polymorphism along with the levels of serum inflammatory (CRP, TNF-α) and anti-inflammatory (IL-10) markers, pro-angiogenic (angiogenin) and anti-angiogenic interferon gamma-induced protein 10 (IP-10) factors as well as adhesion molecules (ICAM-1, ICAM-3). RESULTS: We did not find significant association between T1D and KL-VS alleles. However, we observed that the incidence of KL-VS genotype is lower in a group with retinopathy in comparison to diabetic patients without this complication. Moreover, we established that KL-VS carriers had the lowest levels of inflammatory markers, pro-angiogenic factors and adhesion molecules. Simultaneously, the KL-VS carriers had increased serum levels of anti-inflammatory and anti-angiogenic cytokines than holders bearing wild type genotype. CONCLUSIONS: In conclusion, the findings of our studies suggest that the functional KL-VS variant of the KLOTHO gene protects against the development of retinopathy in patients with T1D.
BACKGROUND AND AIMS: KLOTHO is an anti-ageing circulating hormone involved in insulin signaling, inflammation and vascular homeostasis through its protective effects on the endothelium and antioxidant actions. The common functional "KL-VS" variant of the KLOTHO gene is reproducibly associated with longevity in humans. Large number of studies have evaluated close relationship between KLOTHO protein and diabetes but the association between KL-VS variant and retinopathy in type 1 diabetes mellitus (T1D) is unknown. Therefore, in the present study we examined the association between the KL-VS polymorphism and the risk of diabetic retinopathy (DR) in patients with T1D. METHODS: We examined 400 patients with T1D and 350 healthy age-matched controls. The analysis concerned KL-VS polymorphism along with the levels of serum inflammatory (CRP, TNF-α) and anti-inflammatory (IL-10) markers, pro-angiogenic (angiogenin) and anti-angiogenic interferon gamma-induced protein 10 (IP-10) factors as well as adhesion molecules (ICAM-1, ICAM-3). RESULTS: We did not find significant association between T1D and KL-VS alleles. However, we observed that the incidence of KL-VS genotype is lower in a group with retinopathy in comparison to diabeticpatients without this complication. Moreover, we established that KL-VS carriers had the lowest levels of inflammatory markers, pro-angiogenic factors and adhesion molecules. Simultaneously, the KL-VS carriers had increased serum levels of anti-inflammatory and anti-angiogenic cytokines than holders bearing wild type genotype. CONCLUSIONS: In conclusion, the findings of our studies suggest that the functional KL-VS variant of the KLOTHO gene protects against the development of retinopathy in patients with T1D.
Authors: Jéssica V G F Batista; Diego A Pereira-Martins; Diego A Falcão; Igor F Domingos; Gabriela S Arcanjo; Betânia L Hatzlhofer; Isabel Weinhäuser; Thais H C Batista; Pablo R G Cardoso; Ana C Dos Anjos; Manuela F Hazin; Maira G R Pitta; Fernando F Costa; Aderson S Araujo; Antonio R Lucena-Araujo; Marcos A Bezerra Journal: Ann Hematol Date: 2021-06-14 Impact factor: 3.673