Stromal cell-derived factor-1-30A polymorphism is associated with decreased risk of myocardial infarction and early endothelial disturbance

Aim: Genome-wide association studies have identified single-nucleotide polymorphisms at the 10q11 locus as risk factors for myocardial infarction (MI). This locus lies upstream (80 kb) of the stromal cell-derived factor-1 (SDF1) gene that codes for a chemokine with protective atherogenetic effects and with a major role in the mobilization, homing, and differentiation of endothelial progenitor cells (EPCs). The purpose of this study was to investigate the possible association of SDF1-3'A polymorphism, that upregulates SDF1 protein expression, with MI as well as early endothelial dysfunction and atherosclerosis in young healthy subjects. Methods: 200 patients (181 men age 57.3+/-7.7 years) and 230 healthy controls (96 men, age 52+/-11.9 years) were recruited to investigate the association between MI and SDF1-30A polymorphism. The relationship between SDF1-3'A polymorphism, brachial artery flow-mediated dilation, and the number of circulating EPCs was examined in 50 healthy young adults. Results: A significant difference in SDF1-3'A genotype distribution was observed between patients and controls (P=0.006). Patients carrying the A allele had a significantly reduced MI risk compared with subjects with GG genotype (odds ratio=0.5, 95% CI=0.3-0.9, P=0.001). SDF1-3'A polymorphism presented a significant interaction with other cardiovascular risk factors (Pinteraction<0. 0001). Controls carrying the A allele showed significantly higher flow-mediated dilation (13.9+/-4.9 vs 10.8+/-4.3, P=0.03) and significantly higher values of EPCs (0.029+/-0.009 vs 0.022+/-0.008, P=0.02) compared with GG homozygotes. Conclusion: SDF1-3'A polymorphism is associated with a decreased risk of MI and early endothelial dysfunction, strongly confirming the important atherogenic role of the SDF1 gene at the clinical level.