title: Stromal cell-derived factor-1-3'A polymorphism is associated with decreased risk of myocardial infarction and early endothelial disturbance.
abstract: OBJECTIVE
  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.
  
  
  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 SDF1-3'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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Physiology, CNR, via Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Borghini
authors.forename: Silverio
authors.initials: S
authors.lastname: Sbrana
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vecoli
authors.forename: Antonella
authors.initials: A
authors.lastname: Mercuri
authors.forename: Stefano
authors.initials: S
authors.lastname: Turchi
authors.forename: Clara
authors.initials: C
authors.lastname: Carpeggiani
authors.forename: Antonio
authors.initials: A
authors.lastname: L'Abbate
authors.forename: Maria G
authors.initials: MG
authors.lastname: Andreassi
mesh_terms: D000328:Adult; D000368:Aged; D001916:Brachial Artery / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000235:genetics*; D066026:Endothelial Progenitor Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D015854:Up-Regulation; D014664:Vasodilation / Q000235:genetics / Q000502:physiology
chemical_list: D054377:Chemokine CXCL12