Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Valls, Joan ; Perez-Guallar, Carles ; Cambray, Serafi ; Perez-Guallar, Carles ; Bozic, Milica ; Bermudez-Lopez, Marcelino ; Fernandez, Elvira ; Betriu, Angels ; Rodriguez, Isabel ; Valdivielso, Jose M. ; Aladren Regidor, Ma Jose ; Almirall, Jaume ; Ponz, Esther ; Arteaga Coloma, Jesus ; Bajo Rubio, Ma Auxiliadora ; Diaz, Raquel Raquel ; Belart Rodriguez, Montserrat ; Gascon, Antonio ; Bover Sanjuan, Jordi ; Bronsoms Artero, Josep ; Cabezuelo Romero, Juan B. ; Muray Cases, Salome ; Calvino Varela, Jesus ; Caro Acevedo, Pilar ; Carreras Bassa, Jordi ; Cases Amenos, Aleix ; Masso Jimenez, Elisabet ; Moreno Lopez, Rosario (Universidad de Zaragoza) ; Cigarran Guldris, Secundino ; Lopez Prieto, Saray ; Comas Mongay, Lourdes ; Comerma, Isabel ; Compte Jove, Ma Teresa ; Cuberes Izquierdo, Marta ; de Alvaro, Fernando ; Hevia Ojanguren, Covadonga ; de Arriba de la Fuente, Gabriel ; del Pino y Pino, Ma Dolores ; Diaz-Tejeiro Izquierdo, Rafael ; Ahijado Hormigos, Francisco ; Dotori, Marta ; Duarte, Veronica ; Estupinan Torres, Sara ; Fernandez Reyes, Ma Jose ; Fernandez Rodriguez, Ma Loreto ; Fernandez, Guillermina ; Galan Serrano, Antonio ; Garcia Canton, Cesar ; Garcia Herrera, Antonio L. ; Garcia Mena, Mercedes ; Gil Sacaluga, Luis ; Aguilar, Maria ; Gorriz, Jose Luis ; Huarte Loza, Emma ; Lerma, Jose Luis ; Liebana Canada, Antonio ; Marin Alvarez, Jesus Pedro ; Martin Alemany, Nadia ; Martin Garcia, Jesus ; Martinez Castelao, Alberto ; Martinez Villaescusa, Maria ; Martinez, Isabel ; Moina Eguren, Inigo ; Moreno Los Huertos, Silvia ; Mouzo Mirco, Ricardo ; Munar Vila, Antonia ; Munoz Diaz, Ana Beatriz ; Navarro Gonzalez, Juan F. ; Nieto, Javier ; Carreno, Agustin ; Novoa Fernandez, Enrique ; Ortiz, Alberto ; Fernandez, Beatriz ; Paraiso, Vicente ; Perez Fontan, Miguel ; Peris Domingo, Ana ; Pinera Haces, Celestino ; Prados Garrido, Ma Dolores ; Prieto Velasco, Mario ; Puig Mari, Carmina ; Rivera Gorrin, Maite ; Rubio, Esther ; Ruiz, Pilar ; Salgueira Lazo, Mercedes ; Martinez Puerto, Ana Isabel ; Sanchez Tomero, Jose Antonio ; Sanchez, Jose Emilio ; Sans Lorman, Ramon ; Saracho, Ramon ; Sarrias, Maria ; Seron, Daniel ; Soler, Maria Jose ; Barrios, Clara ; Sousa, Fernando ; Toran, Daniel ; Tornero Molina, Fernando ; Uson Carrasco, Jose Javier ; Valera Cortes, Ildefonso ; Vilaprinyo del Perugia, Ma Merce ; Virto Ruiz, Rafael C. ; Santos Altozano, Carlos ; Artigao Rodenas, Miguel ; Gil Gil, Ines ; Adan Gil, Francisco ; Garcia Criado, Emilio ; Dura Belinchon, Rafael ; Fernandez Toro, Jose Ma ; Divison Garrote, Juan Antonio

Resumen: Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD.

Idioma: Inglés

DOI: 10.3389/fgene.2019.00118

Año: 2019

Publicado en: Frontiers in Genetics 10 (2019), 118 [10 pp]
ISSN: 1664-8021

Factor impacto JCR: 3.258 (2019)

Categ. JCR: GENETICS & HEREDITY rank: 73 / 177 = 0.412 (2019) - Q2 - T2

Factor impacto SCIMAGO: 1.469 - Molecular Medicine (Q1) - Genetics (Q2) - Genetics (clinical) (Q2)

Financiación: info:eu-repo/grantAgreement/ES/AbbVie-FEDER-ISCIII/FIS-PI10-00173
Financiación: info:eu-repo/grantAgreement/ES/AbbVie-FEDER-ISCIII/FIS-PI16-01354
Financiación: info:eu-repo/grantAgreement/ES/AbbVie-FEDER-ISCIII/RETIC-RD16-0009-NEFRONA

Tipo y forma: Article (Published version)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)