Association of carotid atheroma plaque with IL-18 levels and with polymorphisms in the IL-18 receptor gene in a Mediterranean population

Ana Palanca , Amparo Bartual-Rodrigo , Carolina Cuenca , Oscar D. Mayo-López , F. Javier Ampudia-Blasco , Herminia González-Navarro , Juan F. Ascaso , Ana Bárbara García-García , F. Javier Chaves , José T. Real , Sergio Martínez-Hervás
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Abstract

Background

Atherosclerosis is an inflammatory disease. Interleukin 18 (IL-18) is an inflammatory molecule that has been linked to the development of atherosclerosis and cardiovascular disease.

Objective

To evaluate the possible relationship between plasma levels of IL-18 and the presence of atherosclerosis evaluated at the carotid level, as well as to analyze the possible modulation by different polymorphisms in a Mediterranean population.

Material and methods

746 individuals from the metropolitan area of ​​Valencia were included, recruited over a period of 2 years. Hydrocarbon and lipid metabolism parameters were determined using standard methodology and IL-18 using ELISA. In addition, carotid ultrasound was performed and the genotype of 4 SNPs related to the IL-18 signaling pathway was analyzed.

Results

Patients with higher plasma levels of IL-18 had other associated cardiovascular risk factors. Elevated IL-18 levels were significantly associated with higher carotid IMT and the presence of atheromatous plaques. The genotype with the A allele of the SNP rs2287037 was associated with a higher prevalence of carotid atheromatous plaque. On the contrary, the genotype with the C allele of the SNP rs2293224 was associated with a lower prevalence of atheromatous plaque.

Conclusions

High levels of IL-18 were significantly associated with a higher carotid IMT and the presence of atheromatous plaques, which appear to be influenced by genetic factors, as evidenced by associations between SNPs in the IL-18 receptor gene and the presence of atheroma plaque.

地中海地区人群中颈动脉粥样斑块与 IL-18 水平及 IL-18 受体基因多态性的关系
背景动脉粥样硬化是一种炎症性疾病。目的 评估血浆中 IL-18 水平与颈动脉粥样硬化之间可能存在的关系,并分析地中海地区人群中不同多态性可能产生的调节作用。采用标准方法测定碳氢化合物和脂质代谢参数,采用 ELISA 方法测定 IL-18。此外,还进行了颈动脉超声检查,并分析了与 IL-18 信号通路相关的 4 个 SNPs 的基因型。IL-18水平升高与颈动脉内中膜厚度升高和动脉粥样斑块的存在明显相关。带有 SNP rs2287037 的 A 等位基因的基因型与较高的颈动脉粥样斑块发病率相关。结论高水平的 IL-18 与较高的颈动脉内中膜厚度和动脉粥样斑块的存在显著相关,这似乎受到遗传因素的影响,IL-18 受体基因中的 SNP 与动脉粥样斑块的存在之间的关联就证明了这一点。
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