Klotho: its various functions and association with sickle cell disease subphenotypes

The Klotho protein, whose gene has predominant renal expression, acts in the control of serum phosphorus and 1,25-dihydroxyvitamin D3 and regulates the function of ion channels. It also participates in the mechanism of protection against oxidative stress and acts on the vascular endothelium by inducing the production of nitric oxide. Mutations that reflect defects in the Klotho gene expression may be implicated in the onset of osteonecrosis, priapism, and leg ulcers in patients with sickle cell disease, as a result of oxidative stress and endothelial impairment, important factors in the development and severity of this disease. Previous reports regarding the association of Klotho single nucleotide polymorphisms with sickle cell disease subphenotypes have found that these polymorphisms are important to identify genetic markers of risk in these individuals and allow early and more effective therapeutic intervention.

Vitamin D; Oxidative stress; Sickle cell disease; Endothelium; Gene polymorphism