SDF1 Polymorphisms Influence Outcome in Patients with Symptomatic Cardiovascular Disease

PLoS One. 2016 Sep 8;11(9):e0161933. doi: 10.1371/journal.pone.0161933. eCollection 2016.

Abstract

Background: SDF1 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 results: Genotyping 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).

Conclusion: Distinct 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.

MeSH terms

  • Aged
  • Alleles
  • Cardiovascular Diseases / genetics*
  • Chemokine CXCL12 / genetics*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Haplotypes / genetics
  • Homozygote
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Proportional Hazards Models
  • Treatment Outcome

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12

Grants and funding

This work was supported in part by the German Ministry of Education and Research, the Deutsche Forschungsgemeinschaft (Grant Number: BO 3786/1-1), the Robert Bosch Stiftung Stuttgart, the Open Access Publishing Fund of the University of Tuebingen and the Klinische Forschergruppe KFO274 (Grant number 2133-0-0; SCHW858/1-1/2) ‘Platelets-Basic Mechanisms and Translational Implications’. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.