Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemia
Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemia
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DOI：
10.1111/j.1365-2796.2007.01791.x
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发表时间：
2007-07-01
影响因子：
11.1
通讯作者：
Pola, R.
中科院分区：
文献类型：
--
作者：
Flex, A.;Gaetani, E.;Pola, R.
目标。编码炎症分子的基因中的单核苷酸多态性可能决定与心血管疾病发生和进展风险增加相关的遗传谱。在这项研究中，我们评估了外周动脉闭塞性疾病（PAOD）和严重肢体缺血（CLI）受试者中一组功能重要的编码原型炎症分子的基因多态性的分布和相互作用。我们还研究了这些促炎基因多态性之间的协同相互作用是否影响 PAOD 和 CLI 的风险。设计、主题和方法。在一项包括 157 名 PAOD 患者和 206 名对照者的遗传关联研究中，分析了以下基因多态性：C 反应蛋白 (CRP) 1059 G/C、白细胞介素 6 (IL-6)-174 G/C、巨噬细胞迁移抑制因子 (MIF)-173 G/C、单核细胞趋化蛋白 (MCP-1) - 2518 A/G、 E-选择素（E-Sel）Ser128Arg、细胞间粘附分子-1（ICAM-1）469 E/K、基质金属蛋白酶（MMP）-1 -1607 1G/2G、MMP-3-1171 5A/6A和MMP-9-1563 C/T。结果：我们发现IL-6、E-sel、ICAM-1、 MCP-1、MMP-1和MMP-3基因多态性与PAOD显着且独立相关。我们还发现，这些促炎性多态性决定了与不同 PAOD 和 CLI 风险水平相关的基因谱，具体取决于特定个体伴随携带的高风险基因型的数量。结论：促炎性基因谱在 PAOD 受试者中明显更常见。促炎基因型之间的协同作用可能是动脉粥样硬化性疾病的存在和严重程度的潜在标志。
Objectives. Single nucleotide polymorphisms in genes encoding inflammatory molecules may determine genetic profiles associated with increased risk of development and progression of cardiovascular diseases. In this study, we evaluated distribution and reciprocal interaction of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in subjects with peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI). We also investigated whether synergistic interactions between these pro-inflammatory gene polymorphisms influence the risk of PAOD and CLI.Design, subjects and methods. In a genetic association study that included 157 PAOD patients and 206 controls, the following gene polymorphisms were analysed: C-reactive protein (CRP) 1059 G/C, interleukin-6 (IL-6)-174 G/C, macrophage migration inhibitory factor (MIF)-173 G/C, monocyte chemoattractant protein (MCP-1) - 2518 A/G, E-selectin (E-Sel) Ser128Arg, intercellular adhesion molecule-1 (ICAM-1) 469 E/K, matrix metalloproteinase (MMP)-1 -1607 1G/2G, MMP-3-1171 5A/6A and MMP-9-1563 C/T.Results: We found that IL-6, E-sel, ICAM-1, MCP-1, MMP-1 and MMP-3 gene polymorphisms were significantly and independently associated with PAOD. We also found that these pro-inflammatory polymorphisms determine genetic profiles that are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes concomitantly carried by a given individual.Conclusions: Pro-inflammatory genetic profiles are significantly more common in subjects with PAOD. Synergistic effects between pro-inflammatory genotypes might be potential markers for the presence and severity of atherosclerotic disorders.