Tag-SNPs in Phospholipase-Related Genes Modify the Susceptibility to Nephrosclerosis and its Associated Cardiovascular Risk.

Nephrosclerosis patients have a high cardiovascular (CV) risk that is very often of more concern than the renal disease itself. We aimed to determine whether variants in phospholipase-related genes, associated with atherosclerosis and CV outcomes in the general population, could constitute biomarkers of nephrosclerosis and/or its associated CV risk. We screened 1,209 nephrosclerosis patients and controls for 86 tag-SNPs that were identified in the , and gene loci. Regression models were utilized to evaluate their effect on several clinical parameters. Most notably, rs10846744 and rs838880 in showed significant odds ratios (OR) of 0.66 (0.51-0.87), = 0.003 and 1.48 (1.11-1.96), = 0.007 for nephrosclerosis risk. and harboured several SNPs associated with atherosclerosis measurements in the patients, namely common carotid intima media thickness (ccIMT), presence of plaques, number of plaques detected and 2-years ccIMT progression (significant -values ranging from 0.0004 to 0.047). Eight SNPs in were independent risk factors for CV events in nephrosclerosis patients. Their addition to a ROC model containing classic risk factors significantly improved its predictive power from AUC = 69.1% (61.4-76.9) to AUC = 79.1% (73.1-85.1%), = 0.047. Finally, rs932476AA and rs6683619AA genotypes were associated with lower CV event-free survival after controlling for confounding variables [49.59 (47.97-51.21) vs. 51.81 (49.93-51.78) months, = 0.041 and 46.46 (41.00-51.92) vs. 51.17 (50.25-52.08) months, = 0.022, respectively]. Variability in phospholipase-related genes play a relevant role in nephrosclerosis and associated atherosclerosis measurements and CV events.