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Inicio Clínica e Investigación en Arteriosclerosis (English Edition) Association of carotid atheroma plaque with IL-18 levels and with polymorphisms ...
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Vol. 36. Issue 4.
Pages 210-217 (July - August 2024)
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Vol. 36. Issue 4.
Pages 210-217 (July - August 2024)
Original article
Association of carotid atheroma plaque with IL-18 levels and with polymorphisms in the IL-18 receptor gene in a Mediterranean population
Asociación de la placa de ateroma carotídea con los niveles plasmáticos de IL-18 y con polimorfismos en el gen del receptor de la IL-18 en la población mediterránea
Ana Palancaa,b, Amparo Bartual-Rodrigoa, Carolina Cuencab, Oscar D. Mayo-Lópezb, F. Javier Ampudia-Blascoa,b,d,e, Herminia González-Navarrob,c,d, Juan F. Ascasob,e, Ana Bárbara García-Garcíab,d,f, F. Javier Chavesb,d,f, José T. Reala,b,d,e, Sergio Martínez-Hervása,b,d,e,
Corresponding author
smartinezhervas@hotmail.com

Corresponding author.
a Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valencia, Valencia, Spain
b INCLIVA, Instituto de Investigación Sanitaria, Valencia, Spain
c Departamento de Bioquímica y Biología Molecular, Universitat de València, Valencia, Spain
d CIBER de Diabetes y Enfermedades Metabólicas asociadas, Instituto de Salud Carlos III, Madrid, Spain
e Departament de Medicina, Universitat de València, Valencia, Spain
f Unidad de Genómica y Diabetes, INCLIVA, Instituto de Investigación Sanitaria, Valencia, Spain
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Tables (6)
Table 1. Population characteristics according to gender.
Table 2. Populations characteristics based on quartiles of plasma IL-18 levels.
Table 3. Correlations between plasma levels of IL-18 and different variables
Table 4. Association between the presence of carotid atheroma plaque and the SNPs of IL-18 adjusted by age and sex.
Table 5. Regression model evaluating independent determinants of carotid IMT (dependent variable).
Table 6. Regression model that evaluates the independent determinants of atheromatous plaque (dependent variable).
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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.

Keywords:
IL-18
Atherosclerosis
Inflammation
Polymorphism
Atheroma plaque
Resumen
Antecedentes

La arteriosclerosis es una enfermedad inflamatoria. La interleucina 18 (IL-18) es una molécula inflamatoria que se ha relacionado con el desarrollo de arteriosclerosis y enfermedad cardiovascular.

Objetivo

Evaluar la posible relación entre los niveles plasmáticos de IL-18 y la presencia de arteriosclerosis evaluada a nivel carotídeo, así como analizar la posible modulación por diferentes polimorfismos en una población mediterránea.

Material y métodos

Se incluyeron 746 individuos procedentes del área metropolitana de Valencia, reclutados durante un período de 2 años. Se determinaron parámetros del metabolismo hidrocarbonado y lipídico mediante metodología estándar e IL-18 mediante ELISA. Además, se realizó ecografía carotídea y se analizó el genotipo de 4 SNPs relacionados con la vía de señalización de IL-18.

Resultados

Los pacientes con niveles plasmáticos más elevados de IL-18 presentaron otros factores de riesgo cardiovascular asociados. Los niveles elevados de IL-18 se asociaron de forma significativa con un mayor GIM carotídeo y con la presencia de placas de ateroma. El genotipo con el alelo A del SNP rs2287037 se asoció con mayor prevalencia de placa de ateroma carotídea. Por el contrario, el genotipo con el alelo C del SNP rs2293224 se asoció con una menor prevalencia de placa de ateroma.

Conclusiones

Los niveles elevados de IL-18 se asociaron de forma significativa con un mayor GIM carotídeo y con la presencia de placas de ateroma, que parecen estar influenciados por factores genéticos, como lo demuestran las asociaciones entre los SNPs en el gen del receptor de IL-18 y la presencia de placa de ateroma.

Palabras clave:
IL-18
Arteriosclerosis
Inflamación
Polimorfismo
Placa de ateroma

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