Genetic association study of coronary collateral circulation in patients with coronary artery disease using 22 single nucleotide polymorphisms corresponding to 10 genes involved in postischemic neovascularization.

BACKGROUND: Collateral growth in patients with coronary artery disease (CAD) is highly heterogeneous. Although multiple factors are thought to play a role in collateral development, the contribution of genetic factors to coronary collateral circulation (CCC) is largely unknown. The goal of this study was to assess whether functional single nucleotide polymorphisms (SNPs) in genes involved in vascular growth are associated with CCC. METHODS: 677 consecutive CAD patients were enrolled in the study and their CCC was assessed by the Rentrop method. 22 SNPs corresponding to 10 genes involved in postischemic neovascularization were genotyped and multivariate logistic regression models were adjusted using clinically relevant variables to estimate odds ratios and used to examine associations of allelic variants, genotypes and haplotypes with CCC. RESULTS: Statistical analysis showed that the HIF1A rs11549465 and rs2057482; VEGFA rs2010963, rs1570360, rs699947, rs3025039 and rs833061; KDR rs1870377, rs2305948 and rs2071559; CCL2 rs1024611, rs1024610, rs2857657 and rs2857654; NOS3 rs1799983; ICAM1 rs5498 and rs3093030; TGFB1 rs1800469; CD53 rs6679497; POSTN rs3829365 and rs1028728; and LGALS2 rs7291467 polymorphisms, as well as their haplotype combinations, were not associated with CCC (p < 0.05). CONCLUSIONS: We could not validate in our cohort the association of the NOS3 rs1799983, HIF1A rs11549465, VEGFA rs2010963 and rs699947, and LGALS2 rs7291467 variants with CCC reported by other authors. A validated SNP-based genome-wide association study is required to identify polymorphisms influencing CCC.

The HIF1A C85T single nucleotide polymorphism influences the number of branches of the human coronary tree.

OBJECTIVES: Hypoxia is required for the development of the cardiovascular system. Tissue adaptation to low oxygen is mediated through hypoxia-inducible factor 1. Hypoxia-driven gradients of vascular endothelial growth factor within the heart drive vessel tip sprouting and the angiogenic phase of vasculogenesis. We hypothesized that functional variants of the HIF1A C85T single nucleotide polymorphism (SNP) are associated with the number of coronary artery branches in humans. METHODS: Coronary artery branching in 88 individuals was assessed by dynamic counting of the arterial branches detected in coronary angiograms. Values were classified on the basis of the branches emerging from the right and left coronary arteries. HIF1A C85T genotypes were determined using TaqMan-based assays. A generalized linear model was used to measure the effect of each SNP on the response variables. RESULTS: The presence of the T allele in the HIF1A C85T SNP was associated with few branches of the coronary arteries: 81.03 ± 1.79 for individuals with the CC genotype versus 74.09 ± 2.48 for T-carrying ones (p = 0.042). CONCLUSIONS: The functionality of HIF1A may influence the degree of branching of the human coronary tree. We propose that the HIF1A C85T SNP is a genetic marker that determines interindividual differences in the human coronary artery pattern.

Cardiac injuries in blunt chest trauma.

Blunt chest traumas are a clinical challenge, both for diagnosis and treatment. The use of cardiovascular magnetic resonance can play a major role in this setting. We present two cases: a 12-year-old boy and 45-year-old man. Late gadolinium enhancement imaging enabled visualization of myocardial damage resulting from the trauma.

The PLAU P141L single nucleotide polymorphism is associated with collateral circulation in patients with coronary artery disease.

INTRODUCTION AND OBJECTIVES: Urokinase-type plasminogen activator, which is encoded by the PLAU gene, plays a prominent role during collateral arterial growth. We investigated whether the PLAU P141L (C > T) polymorphism, which causes a mutation in the kringle domain of the protein, is associated with coronary collateral circulation in a cohort of 676 patients with coronary artery disease. METHODS: The polymorphism was genotyped in blood samples using a TaqMan-based genotyping assay, and collateral circulation was assessed by the Rentrop method. Multivariate logistic regression models adjusted by clinically relevant variables to estimate odds ratios were used to examine associations of PLAU P141L allelic variants and genotypes with collateral circulation. RESULTS: Patients with poor collateral circulation (Rentrop 0-1; n = 547) showed a higher frequency of the TT genotype than those with good collateral circulation (Rentrop 2-3; n = 129; P = .020). The T allele variant was also more common in patients with poor collateral circulation (P = .006). The odds ratio of having poorly developed collaterals in patients bearing the T allele (adjusted for clinically relevant variables) was statistically significant under the dominant model (odds ratio = 1.83 [95% confidence interval, 1.16-2.90]; P = .010) and the additive model (odds ratio = 1.73 [95% confidence interval, 1.14-2.62]; P = .009). CONCLUSIONS: An association was found between coronary collateral circulation and the PLAU P141L polymorphism. Patients with the 141L variant are at greater risk of developing poor coronary collateral circulation.