The KL-VS polymorphism of KLOTHO gene is protective against retinopathy incidence in patients with type 1 diabetes.

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.