SDF1 Polymorphisms Influence Outcome in Patients with Symptomatic Cardiovascular Disease.
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.


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).


CONCLUSIONS
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.
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Dominik
D
Rath
Dr. Margarete-Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, Stuttgart, Germany.
Elke
E
Schaeffeler
Dr. Margarete-Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, Stuttgart, Germany.
Stefan
S
Winter
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Jens
J
Hewer
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Karin
K
Müller
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Michal
M
Droppa
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Fabian
F
Stimpfle
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Meinrad
M
Gawaz
Dr. Margarete-Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, Stuttgart, Germany.|Department of Clinical Pharmacology, University Hospital Tuebingen, Auf der Morgenstelle 8, Tuebingen, Germany.
Matthias
M
Schwab
Department of Cardiology, University Hospital Tuebingen, Otfried-Mueller-Straße 10, Tuebingen, Germany.
Tobias
T
Geisler
D000368:Aged; D000483:Alleles; D002318:Cardiovascular Diseases / Q000235:genetics*; D054377:Chemokine CXCL12 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D016896:Treatment Outcome
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12