Influence of Klotho gene polymorphisms on vascular gene expression and its relationship to cardiovascular disease

• Published in: Journal of cellular and molecular medicine 2016-01, Vol.20 (1), p.128-133
• Main Authors: Donate‐Correa, Javier, Martín‐Núñez, Ernesto, Martínez‐Sanz, Rafael, Muros‐de‐Fuentes, Mercedes, Mora‐Fernández, Carmen, Pérez‐Delgado, Nayra, Navarro‐González, Juan F.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Aortic Valve Stenosis - genetics; Aortic Valve Stenosis - metabolism; Aortic Valve Stenosis - surgery; Arteriosclerosis; Blood pressure; Calcification; Cardiovascular disease; Cardiovascular diseases; Coronary artery; Coronary Artery Bypass; Coronary artery disease; Coronary vessels; Deoxyribonucleic acid; Diabetes; Diabetes mellitus; DNA; Female; Fibroblasts; Gene expression; Genetic Association Studies; Genetic Predisposition to Disease; Glucuronidase - genetics; Growth factors; Health risk assessment; Health risks; Heart diseases; Heart Valve Diseases - genetics; Heart Valve Diseases - metabolism; Heart Valve Diseases - surgery; Heart Valve Prosthesis Implantation; Humans; Incidence; Klotho; Klotho protein; Klotho Proteins; Male; Middle Aged; Original; Polymorphism, Single Nucleotide; Proteins; Risk Factors; single nucleotide polymorphisms; Software; Statistical analysis; Studies; Surgery; Transcriptome; Vascular diseases; vascular expression
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12710

Klotho protein has been associated with beneficial effects that contribute to the maintenance of cardiovascular health. Diverse studies suggest that alterations in the levels of this molecule may be associated with pathophysiological abnormalities that result in increased cardiovascular risk. The primary aim of this proof‐of‐concept study was to analyse the existence of a potential link between Klotho gene polymorphisms and the expression level of this gene in the vascular wall, and additionally with the incidence of cardiovascular disease and cardiovascular risk factors. Our results indicate that the variant G‐395A, located in the promoter region, influences Klotho gene vascular expression and is associated with the incidence of diabetes. Similarly, the exonic variant KL‐VS was associated with the incidence of atherosclerotic vascular disease and coronary artery disease. Moreover, vascular expression levels of Klotho were related with the incidence of diabetes mellitus and coronary artery disease. These findings, which need to be confirmed in larger studies, suggest a potential role of Klotho in the pathogenesis of vascular damage.