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首页> 外文期刊>Human Heredity >Inflammatory gene haplotype-interaction networks involved in coronary collateral formation.
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Inflammatory gene haplotype-interaction networks involved in coronary collateral formation.

机译：参与冠状动脉侧支形成的炎性基因单倍型相互作用网络。

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摘要

OBJECTIVES: Formation of collateral circulation is an endogenous response to atherosclerosis, and is a natural escape mechanism by re-routing blood. Inflammatory response- related genes underlie the formation of coronary collaterals. We explored the genetic basis of collateral formation in man postulating interaction networks between functional Single Nucleotide Polymorphisms (SNPs) in these inflammatory gene candidates. METHODS: The contribution of 41 genes as well as the interactions among them was examined in a cohort of 226 coronary artery disease patients, genotyped for 54 candidate SNPs. Patients were classified to the extent of collateral circulation. Stepwise logistic regression analysis and a haplotype entropy procedure were applied to search for haplotype interactions among all 54 polymorphisms. Multiple testing was addressed by using the false discovery rate (FDR) method. RESULTS: The population comprised 84 patients with and 142 without visible collaterals. Among the 41 genes, 16 pairs of SNPs were implicated in the development of collaterals with the FDR of 0.19. Nine SNPs were found to potentially have main effects on collateral formation. Two sets of coupling haplotypes that predispose to collateral formation were suggested. CONCLUSIONS: These findings suggest that collateral formation may arise from the interactions between several SNPs in inflammatory response related genes, which may represent targets in future studies of collateral formation. This may enhance developing strategies for risk stratification and therapeutic stimulation of arteriogenesis.
机译：目的：侧支循环的形成是对动脉粥样硬化的内源性反应，并且是通过重新路由血液而自然逃逸的机制。炎症反应相关基因是冠状动脉侧支形成的基础。我们探讨了在这些炎症基因候选物中功能性单核苷酸多态性（SNP）之间的相互作用网络中人侧支形成的遗传基础。方法：在226例冠状动脉疾病患者队列中检查了41个基因的贡献以及它们之间的相互作用，对54个候选SNPs进行了基因分型。根据侧支循环程度对患者进行分类。应用逐步逻辑回归分析和单倍型熵程序来搜索所有54个多态性之间的单倍型相互作用。通过使用错误发现率（FDR）方法解决了多次测试。结果：该人群包括84例有142例无明显侧支的患者。在这41个基因中，有16对SNP与FDR为0.19的抵押品发生有关。发现9个SNP对侧支形成有潜在的主要影响。建议使用两组容易形成侧枝的偶合单倍型。结论：这些发现表明，侧支形成可能是由炎症反应相关基因中的几个SNP之间的相互作用引起的，这可能是将来侧支形成研究的目标。这可能会增强风险分层和对动脉生成的治疗性刺激的开发策略。

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