SDF1 Polymorphisms Influence Outcome in Patients with Symptomatic Cardiovascular Disease

Abstract

BackgroundSDF1 and its cognate receptors CXCR4 and CXCR7 are involved in myocardial repair and are associated with outcome in cardiovascular patients. Hence, we aimed to investigate clinically significant SDF1 SNPs for their prognostic impact in patients with cardiovascular disease.Methods and ResultsGenotyping for selected SDF1 variants (rs1065297, rs2839693, rs1801157, rs266087, rs266085 and rs266089 was performed in patients (n = 872) who underwent percutaneous coronary intervention. Carriers of variant rs2839693 and rs266089 showed significantly higher cumulative event-free survival compared with non-carriers. All other polymorphisms had no relevant influence on outcome. Multivariate Cox regression analysis showed a significant correlation of these SNPs with cardiovascular outcome after inclusion of clinical and prognostic relevant variables (hazard ratio (HR) 0.51 (95% CI 0.30–0.88), p = 0.015 and [HR 0.51 (95% CI 0.30–0.88), p = 0.016, respectively). In addition, multivariate Cox regression with SDF1 haplotypes revealed a significantly reduced risk for the haplotype carrying the minor alleles of rs2839693 and rs266089 (HR 0.47 (95% CI 0.27–0.84), p = 0.011).ConclusionDistinct SDF1 polymorphisms are associated with improved cardiovascular prognosis in CAD patients. Further studies are warranted to validate these results and to better describe the endogenous regeneration potential in carriers of these SNPs. Targeted, genotype guided therapeutic approaches to foster myocardial regeneration and thus cardiovascular prognosis should be evaluated in future.

Variants in the CXCL12 gene was associated with coronary artery disease susceptibility in Chinese Han population

“…We also found that rs266089 in CXCL12 gene increased the CAD risk in total population and in men; rs2839693 in CXCL12 gene associated with the risk of CAD in men. A study explored the SDF1 SNPs for prognostic impact in patients with cardiovascular disease, found that cardiovascular who were SDF1 rs2839693 and rs266089 minor allele carriers showed a significantly better event-free survival probability compared to homozygote carriers of major allele [ 17 ]. Apart from this, an article reported that homozygous genotype of the minor allele of rs2839693, A/A, was shown to be significantly decreased in ITP patients, which suggested a protective role of these genotypes [ 18 ].…”

“…We selected candidate SNPs of CXCL12 according to previous published papers which demonstrated association with CAD in other ethnic lines and only MAF>5% in the Hapmap Asian population were valid [ 17 ]. Finally, a number of 6 SNPs were chosen for further analysis.…”

Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer

“…As already touched upon, retrospective clinical data might hint to associations between SDF-1 polymorphisms or SDF-1/CXCR4 expression levels with susceptibility to neoplastic transformation, malignant progression or therapy response in a variety of tumor entities, such as renal cell carcinoma (97), prostate cancer (98), HNSCC (1, 100, 102, 113, 114), esophagogastric cancer (103), hepatocellular carcinoma (104), colorectal cancer (74), breast cancer (153), osteosarcoma (111), low grade glioma (154, 155), or GBM (156, 157). Beyond cancer SDF-1 genetics has been associated with e.g., the pathogenesis of multiple sclerosis (158) or prognosis in patients with cardiovascular disease (159).…”

GPla Polymorphisms Are Associated with Outcomes in Patients at High Cardiovascular Risk

“…GP Ia SNP analysis was performed in a previously described cohort of 943 consecutive patients with stable CAD and ACS including non-ST-elevation myocardial infarction and ST-elevation myocardial infarction ( 18 ). CAD was defined as narrowing of at least one coronary artery ≥50% ( 19 ).…”

“…Genotyping for this GP Ia variants was performed as previously described by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) using the MassARRAY ® Compact system (Sequenom, CA, USA) ( 18 ). Study personnel assessing outcome was blinded to the case status of the study participants during the entire genotyping process.…”