1. Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease
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Cambray S., Bermudez-Lopez M., Bozic M., Valdivielso J.M., Castro E., María V., Molí T., Vidal T., Soria M., Aladrén Regidor Ma.J., Almirall J., Ponz E., Arteaga Coloma J., Bajo Rubio Ma.A., Belart Rodríguez M., Gascón A., Bover Sanjuan J., Puigvert F., Bronsoms Artero J., Cabezuelo Romero J.B., Muray Cases S., Calviño Varela J., Caro Acevedo P., Carreras Bassa J., Cases Amenós A., Massó Jiménez E., Moreno López R., Cigarrán Guldris S., López Prieto S., Comas Mongay L., Comerma I., Compte Jové Ma.T., Cuberes Izquierdo M., de Álvaro F., Hevia Ojanguren C., de Arriba de la Fuente G., del Pino y Pino Ma.D., Diaz-Tejeiro Izquierdo R., Hormigos A., Dotori M., Duarte V., Estupiñan Torres S., Fernández Reyes Ma.J., Fernández Rodríguez Ma.L., Fernández G., Galán Serrano A., García Cantón C., García Herrera A.L., García Mena M., Gil Sacaluga L., Aguilar M., Górriz J.L., Huarte Loza E., Lerma J.L., Liebana Cañada A., Marín Álvarez J.P., Martín Alemany N., Martín García J., Martínez Castelao A., Martínez Villaescusa M., Martínez I., Moina Eguren I., Moreno Los Huertos S., Mouzo Mirco R., Munar Vila A., Muñoz Díaz A.B., Navarro González J.F., Nieto J., Carreño A., Novoa Fernández E., Ortiz A., Fernandez B., Paraíso V., Pérez Fontán M., Peris Domingo A., Piñera Haces C., Prados Garrido Ma.D., Prieto Velasco M., Puig Marí C., Rivera Gorrín M., Rubio E., Ruiz P., Salgueira Lazo M., Martínez Puerto A.I., Sánchez Tomero J.A., Sánchez J.E., Sans Lorman R., Saracho R., Sarrias M., Serón D., Soler M.J., Barrios C., Sousa F., Toran D., Tornero Molina F., Usón Carrasco J.J., Valera Cortes I., Vilaprinyo del Perugia Ma.M., Ruiz V., Pallarés V., Altozano C.S., Ródenas M.A., Sanitaria de Arán I.G.G.Á.B., Gil F.A., Criado E.G., Belinchón R.D., Fernández Toro J.Ma., and Antonio J.
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cardiovascular risk ,genetic association ,adult ,genotype ,allele ,chronic kidney failure ,cohort analysis ,major clinical study ,Klotho protein ,Article ,homozygote ,aged ,cause of death ,female ,multicenter study ,male ,priority journal ,cardiovascular mortality ,single nucleotide polymorphism ,follow up ,human ,prospective study - Abstract
Background. Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. Methods. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). Results. After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10-6 (95% CI 3.3 × 10-7-1.1 × 10-5)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Conclusions. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD. © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
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- 2020
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