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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00118

ASSOCIATION OF CANDIDATE GENE POLYMORPHISMS WITH CHRONIC KIDNEY DISEASE: RESULTS OF A CASE-CONTROL ANALYSIS IN THE NEFRONA COHORT

Joan Valls1,  Serafi Cambray1,  Carles Pérez-Guallar1,  Milica Bozic1, Marcelino Bermudez-Lopez1, Elvira Fernandez1,  Angels Betriu1,  Isabel Rodriguez2 and  Jose M. Valdivielso1*
  • 1Institut de Recerca Biomedica de Lleida (IRBLleida), Spain
  • 2Central University Hospital of Asturias, Spain

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 analysed the genetic association of seventy-nine 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 ionization–time 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 SNP (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, ostecalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of sufferin CKD.

Keywords: Chronic Kidney Disease, Mineral metabolism and bone disease, Single nucleotide polymorphism, Risk factors, Association study, case-control study, essential hypertension, homocysteine, ischemic stroke

Received: 10 Jul 2018; Accepted: 04 Feb 2019.

Edited by:

Kelli K. Ryckman, The University of Iowa, United States

Reviewed by:

Martha Guevara-Cruz, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico
Bethany Wolf, Medical University of South Carolina, United States  

Copyright: © 2019 Valls, Cambray, Pérez-Guallar, Bozic, Bermudez-Lopez, Fernandez, Betriu, Rodriguez and Valdivielso. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Jose M. Valdivielso, Institut de Recerca Biomedica de Lleida (IRBLleida), Lleida, Spain, valdivielso@medicina.udl.es