Matrix Gla protein polymorphism rs1800802 is associated with atheroma plaque progression and with cardiovascular events in a chronic kidney disease cohort
Authors: Cambray Serafí , Bermúdez-López Marcelino , Garcia-Carrasco Alicia , Valdivielso Jose M ,   NEFRONA investigators, Aladrén Regidor Mª José , Almirall Jaume , Ponz Esther , Coloma Jesús Arteaga , Rubio Bajo , Aladrén Regidor Mª José , Rodríguez Belart , Gascón Antonio , Sanjuan Jordi Bover , Artero Josep Bronsoms , Cabezuelo Romero Juan B , Cases Muray , Calviño Varela Jesús , Acevedo Pilar Caro , Bassa Jordi Carreras , Amenós Aleix Cases , Jiménez Elisabet Massó , López Rosario Moreno , Guldris Secundino Cigarrán , Prieto Saray López , Mongay Lourdes Comas , Comerma Isabel , Compte Jové Mª Teresa , Izquierdo Marta Cuberes , de Álvaro Fernando , Hevia Ojanguren Covadonga , de Arriba de la Fuente Gabriel , del Pino y Pino Mª Dolores , Diaz-Tejeiro Izquierdo Rafael , Dotori Marta , Duarte Verónica , Estupiñan Torres Sara , Fernández Reyes Mª José , Fernández Rodríguez Mª Loreto , Fernández Guillermina , Galán Serrano Antonio , García Cantón Cesar , García Herrera Antonio L , García Mena Mercedes , Gil Sacaluga Luis , Górriz José Luis , Huarte Loza Emma , Lerma José Luis , Liebana Cañada Antonio , Marín Álvarez Jesús Pedro , Martín Alemany Nàdia , Martín García Jesús , Martínez Castelao Alberto , Martínez Villaescusa María , Martínez Isabel , Moina Eguren Iñigo , Moreno Los Huertos Silvia , Mouzo Mirco Ricardo , Munar Vila Antonia , Muñoz Díaz Ana Beatriz , Navarro González Juan F , Nieto Javier , Carreño Agustín , Novoa Fernández Enrique , Ortiz Alberto , Paraíso Vicente , Pérez Fontán Miguel , Peris Domingo Ana , Piñera Haces Celestino , Prados Garrido Mª Dolores , Prieto Velasco Mario , Puig Marí Carmina , Rivera Gorrín Maite , Rubio Esther , Ruiz Pilar , Salgueira Lazo Mercedes , Martínez Puerto Ana Isabel , Sánchez Tomero José Antonio , Sánchez José Emilio , Lorman Ramon Sans , Saracho Ramon , Sarrias Maria , Serón Daniel , Soler María José , Barrios Clara , Sousa Fernando , Toran Daniel , Molina Fernando Tornero , Carrasco José Javier Usón , Cortes Ildefonso Valera , Vilaprinyo del Perugia Mª Merce , Virto Ruiz Rafael C , GilGil Área Básica Sanitaria de Arán Inés , Toro Jose Mª Fernández , Ibáñez Juan Antonio Divisón Garrote Centro de Salud de Casas 
Published: October 2023

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.