Stromal cell-derived factor-1-3'A polymorphism is associated with decreased risk of myocardial infarction and early endothelial disturbance.

Abstract

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 codify 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 and early endothelial dysfunction and atherosclerosis in young healthy subjects. 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 SDF1-3'A polymorphism. The relationship between SDF1-3'A polymorphism and brachial artery flow-mediated dilation and the number of circulating EPCs was examined in 50 healthy young adults. 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. SDF1-3'A polymorphism is associated with a decreased risk of MI and early endothelial dysfunction, strongly confirming the important atherogenic role of SDF1 gene at clinical level.