The rs1126616 Single Nucleotide Polymorphism of the Osteopontin Gene Is Independently Associated with Cardiovascular Events in a Chronic Kidney Disease Cohort

Abstract

Chronic kidney disease (CKD) is associated with a higher risk of cardiovascular events (CVE), partly due to the higher burden of atherosclerosis. Circulating Osteopontin (OPN) levels have been also shown to have a potential role in the development of atherosclerosis. Indeed, CKD patients show an increase in circulating OPN levels, but their effect of CKD-related atherosclerosis is not clear. Polymorphisms in the OPN gene (SPP1) have been studied in atheromatous disease, but reported results show conflictive findings. Thus, the main aim of the present study is to analyze the influence of SPP1 polymorphisms in CVE in CKD patients, taking into account circulating OPN levels. We followed 559 healthy controls and 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology study (NEFRONA study). After 48 months of follow-up 206 CVE were recorded. Genotyping for rs9138, rs1126616, rs1126772, rs11730582 and rs28357094 polymorphisms of the SPP1 gene was performed along with the measurements of plasma OPN levels. The group of patients with CVE showed higher incidence of atherosclerotic plaque (90.3% vs 64.5%; p < 0.001) and higher OPN levels (p < 0.001) at baseline. Patients with the heterozygous genotype of the rs1126616 polymorphism showed a higher hazard ratio of having a CVE, even after adjustment for multiple potential confounders. After adjustment, OPN levels were no longer associated with the incidence of CVE. We found that the rs1126616 single nucleotide polymorphism (SNP) of the SPP1 gene is independently associated with a higher incidence of CVE in a cohort of CKD patients and that it could be used to predict CVE risk.