ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2011
Lack of association of Klotho gene variants with valvular and vascular calcification in Caucasians: a candidate gene study of the Framingham Offspring Cohort.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.PloS one · 2014Trial
- Spatial multiomics atlas reveals smooth muscle phenotypic transformation and metabolic reprogramming in diabetic macroangiopathy.Cardiovascular diabetology · 2024Article
- CYP24A1 and KL polymorphisms are associated with the extent of vascular calcification but do not improve prediction of cardiovascular events.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021Article
- Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease.Clinical kidney journal · 2020Article
- KLOTHO polymorphisms and age-related outcomes in community-dwelling older subjects: The São Paulo Ageing & Health (SPAH) Study.Scientific reports · 2020Article
- Antiaging Factor Klotho Retards the Progress of Intervertebral Disc Degeneration through the Toll-Like Receptor 4-NF-International journal of cell biology · 2020Article
- Update on Chronic Kidney Disease Mineral and Bone Disorder in Cardiovascular Disease.Seminars in nephrology · 2018Review
- A Genomics-Based Model for Prediction of Severe Bioprosthetic Mitral Valve Calcification.International journal of molecular sciences · 2016Article
- Influence of Klotho gene polymorphisms on vascular gene expression and its relationship to cardiovascular disease.Journal of cellular and molecular medicine · 2016Article
- The Role and Mechanism of α-Klotho in the Calcification of Rat Aortic Vascular Smooth Muscle Cells.BioMed research international · 2015Article
- Genetic predisposition to calcific aortic stenosis and mitral annular calcification.Molecular biology reports · 2014Review
- Rosiglitazone increases cerebral klotho expression to reverse baroreflex in type 1-like diabetic rats.BioMed research international · 2014Article
- Biochemical and functional characterization of the klotho-VS polymorphism implicated in aging and disease risk.The Journal of biological chemistry · 2013Article
- Renal and extrarenal actions of Klotho.Seminars in nephrology · 2013Review
- The role of Klotho in energy metabolism.Nature reviews. Endocrinology · 2012Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundValvular and vascular calcification are important early aging phenotypes and represent risk factors for cardiovascular morbidity and mortality. Klotho is a gene primarily expressed in the kidney that has an important role in calcium-phosphate homeostasis. The functional KL-VS variant of Klotho has been associated with aging and cardiovascular disease in human studies, but its role in valvular and vascular calcification remains unknown. We performed a candidate gene study in the Framingham Offspring Cohort to evaluate the effect of KL-VS variant of the Klotho gene on valvular calcification.
methodsWe analyzed the Klotho KL-VS genotype (rs9536314) from the Affymetrix 550K genome-wide dataset, distributed by dbGAP, on 1389 cases and 2139 controls from the Framingham Heart Study Offspring Cohort. Allele and genotype frequencies were compared between cases and controls. Valvular calcification was defined as presence of calcification on the mitral annulus or the aortic valve as determined by echocardiography. A sensitivity analysis of coronary artery calcification by electron beam computed tomography was performed on 1363 patients.
resultsThe frequency of the TT versus the TG allele was not different between the cases and the controls (39 versus 41%). The KL-VS variant of Klotho was not associated with valvular or vascular calcification, despite adequate power to detect association (86% for odds ratios ≥1.2). In sensitivity analyses, no association (P > 0.001) between other common variants of Klotho, β-Klotho or fibroblast growth factor-23 and the end points of valvular or vascular calcification was observed.
conclusionsIn our adequately powered candidate gene study, we did not observe an association with the functional KL-VS variant of Klotho and presence of valvular or vascular calcification. Future studies aimed at combining cohorts with echocardiographic phenotypes need to be conducted to identify genetic variants associated with valvular calcification.
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