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Matrix Gla protein polymorphism rs1800802 is associated with atheroma plaque progression and with cardiovascular events in a chronic kidney disease cohort

2023; Oxford University Press; Volume: 17; Issue: 1 Linguagem: Inglês

10.1093/ckj/sfad257

2048-8513

Serafí Cambray, Marcelino Bermúdez-López, Alicia García-Carrasco, José Manuel Valdivielso, Ma José Aladrén Regidor, Jaume Almirall, Esther Ponz, Jesús Arteaga Coloma, M. Auxiliadora Bajo, Ma José Aladrén Regidor, Belart Rodríguez, Antonio Gascón, Jordi Bover Sanjuán, Josep Bronsoms Artero, J.B. Cabezuelo, Muray Cases, Jesús Calviño Varela, Pilar Caro Acevedo, Jordi Carreras Bassa, Aleix Cases, Elisabet Massó Jiménez, Rosario Moreno López, Secundino Cigarrán, Saray López Prieto, Lourdes Comas Mongay, Isabel Comerma, Ma Teresa Compte Jové, Marta Cuberes Izquierdo, Fernando de Álvaro, Covadonga Hevia Ojanguren, Gabriel de Arriba, María Dolores del Pino y Pino, Rafael Diaz-Tejeiro Izquierdo, Marta Dotori, Verónica Duarte, Sara Estupiñan Torres, María José Fernández‐Reyes, Ma Loreto Fernández Rodríguez, Guillermina Fernández, Antonio Galán Serrano, César García Cantón, Antonio Luis García Herrera, Mercedes García Mena, Luis Gil Sacaluga, José Luis Górriz, Emma Huarte Loza, José Luis Lerma, A. Cañada, Jesús Pedro Marín Álvarez, Nàdia Martín Alemany, Jesús Martín García, Alberto Martínez Castelao, María Martínez Villaescusa, Isabel Martínez, Itsaso Larrabide Eguren, Silvia Moreno Los Huertos, Ricardo Mouzo Mirco, Antonia Munar Vila, Ana Beatriz Muñoz Díaz, Juan F. Navarro‐González, Javier Nieto, Agustín Carreño, Enrique Novoa Fernández, Alberto Ortíz, Vicente Paraíso, Miguel Pérez Fontán, Ana Peris Domingo, Celestino Piñera Haces, Ma Dolores Prados Garrido, Mario Prieto Velasco, Carmina Puig Marí, Maite Rivera, Eduardo Rubio González, M. Pilar Ruiz, Mercedes Salgueira Lazo, Ana Isabel Martínez Puerto, José Antonio Sánchez Tomero, José Emilio Hernández Sánchez, Ramon Sans Lorman, Ramón Saracho, Maria‐Rosa Sarrias, Daniel Serón, María José Soler, Clara Barrios, Fernando Henrique Sousa, D Torán, Fernando Tornero Molina, José Javier Usón Carrasco, Ildefonso Valera Cortes, Ma Merce Vilaprinyo del Perugia, Rafael C Virto Ruiz, Inés GilGil Área Básica Sanitaria de Arán, Jose Ma Fernández Toro, J Ibáñez,

Folate and B Vitamins Research

ABSTRACT Background Chronic kidney disease (CKD) is associated with increased atherosclerotic burden and higher risk for cardiovascular events (CVE). Atherosclerosis has a significant genetic component and, in CKD, it is influenced by mineral metabolism alterations. Therefore, genetic modifications of mineral metabolism–related proteins could affect atherosclerosis in CKD patients. In the present study we investigated the role of single nucleotide polymorphisms (SNPs) of the matrix gamma-carboxy glutamic acid protein (MGP) on atherosclerosis progression and CVE in a CKD cohort. Methods A total of 2187 CKD patients from the Observatorio Nacional de Aterosclerosis en Nefrologia (NEFRONA) study were genotyped for SNPs present in the matrix gamma-carboxy glutamic acid (Gla) protein (MGP) gene. Atheromatosis was detected by vascular ultrasound. Progression of atheromatosis, defined as an increase in territories with plaque, was assessed after 24 months. Patients were followed for 48 months for CVE. Association of SNPs with plaque progression was assessed by logistic regression and their capacity to predict CVE by Cox regression. Results Three SNPs of the MGP gene were analyzed. No association of the rs4236 or the rs1800801 SNPs was detected with any of the outcomes. However, patients homozygotes for the minor allele of the rs1800802 SNP showed higher adjusted risk for plaque progression [odds ratio 2.3 (95% confidence interval 1.06–4.9)] and higher risk of suffering a CVE [hazard ratio 2.16 (95% confidence interval 1.13–4.12)] compared with the rest of genotypes. No association of the SNP with total or dp-ucMGP levels was found in a subsample. Conclusions The rs1800802 polymorphism of MGP is associated with plaque progression and CVE in CKD patients.