Alonso-Villaverde Carlos, Coll Blai, Parra Sandra, Montero Manuel, Calvo Nahum, Tous Mònica, Joven Jorge, Masana Lluis
Servei de Medicina Interna, Hospital Universitari de Sant Joan, 43201 Reus, Spain.
Circulation. 2004 Oct 12;110(15):2204-9. doi: 10.1161/01.CIR.0000143835.95029.7D. Epub 2004 Oct 4.
Patients infected with HIV present with premature atherosclerosis, and the 2 diseases share common pathogenic pathways. We investigated mutations in the monocyte chemoattractant protein-1 (MCP-1) and CCR-2 genes, which are known to control aspects of these pathways, to ascertain whether they are involved in atherogenesis in these patients.
We performed carotid and femoral artery ultrasonography to detect subclinical atherosclerosis in patients infected with HIV (n=183). MCP-1-2518G and CCR-2 64I polymorphisms were determined in the HIV group and in a population-based control group (n=348). We also determined MCP-1 circulating levels in the HIV group. The presence of MCP-1-2518G in the group of patients with subclinical atherosclerosis was significantly higher than in patients without atherosclerotic lesions (47.5% versus 18.2%, respectively; P<0.001). Furthermore, the patients with atherosclerotic lesions had higher MCP-1 plasma concentrations than did patients without lesions (74.15 [4.03] versus 57.81 [3.67] pg/mL, respectively; P=0.03). When adjusted for known cardiovascular risk factors, the MCP-1-2518G allele was associated with subclinical atherosclerosis (OR 5.72, 95% CI 1.74 to 18.80, P=0.004). Compared with measurements conducted approximately 2.5 years earlier in a subset of 40 patients, intima-media thickness (IMT) in the carotid artery progressed at a mean rate of 0.06 mm/y more rapidly in patients bearing the MCP-1-mutated allele (P=0.08).
HIV-infected patients with the MCP-1-2518G allele have a 5-fold increased risk for atherosclerosis, as assessed by ultrasonography.
感染HIV的患者会出现动脉粥样硬化提前发生的情况，这两种疾病具有共同的致病途径。我们研究了单核细胞趋化蛋白-1（MCP-1）和CCR-2基因的突变情况，已知这些基因控制着这些途径的某些方面，以确定它们是否参与了这些患者的动脉粥样硬化形成过程。
我们对183例感染HIV的患者进行了颈动脉和股动脉超声检查，以检测亚临床动脉粥样硬化情况。在HIV组和一个基于人群的对照组（348例）中测定了MCP-1 -2518G和CCR-2 64I多态性。我们还测定了HIV组中MCP-1的循环水平。亚临床动脉粥样硬化患者组中MCP-1 -2518G的存在率显著高于无动脉粥样硬化病变的患者（分别为47.5%和18.2%；P<0.001）。此外，有动脉粥样硬化病变的患者血浆MCP-1浓度高于无病变的患者（分别为74.15[4.03]和57.81[3.67] pg/mL；P=0.03）。在对已知的心血管危险因素进行校正后，MCP-1 -2518G等位基因与亚临床动脉粥样硬化相关（比值比5.72，95%可信区间1.74至18.80，P=0.004）。与大约2.5年前在40例患者亚组中进行的测量相比，携带MCP-1突变等位基因的患者颈动脉内膜中层厚度（IMT）以平均每年0.06 mm的速度更快进展（P=0.08）。
通过超声检查评估，携带MCP-1 -2518G等位基因的HIV感染患者患动脉粥样硬化的风险增加了5倍。
