期刊
AIDS
卷 32, 期 8, 页码 1035-1041出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000001797
关键词
cardiovascular disease; HIV; monocytes; toll-like receptor 4 Asp299Gly single nucleotide polymorphism
资金
- Redes tematicas de Investigacion en SIDA (Spanish Instituto de Salud Carlos III), Plan Nacional R+D+I [ISCIII RETIC RD12/0017/0029, RD12/0017/0037, RD16/0025/0020]
- ISCIII-Subdireccion General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER) [RETIC PT13/0010/0028]
- FIS [PI13/02016, PI14/00882, PI16/00684]
- Comunidad de Madrid [S-2010/BMD-2351, S-2010/BMD-2332]
- CYTED [214RT0482]
- Programa de Investigacion de la Consejeri a de Sanidad de la CAM
- ISCIII [FI14/00431]
- Fondo de Investigacion Sanitaria through the Miguel Servet'' program [CPII014/00025]
- Consejeria de Salud y Bienestar Social of Junta de Andalucia through the Nicolas Monardes program [C-0032/17]
Objective: Cardiovascular diseases (CVDs) are one of the main causes of morbimortality in HIV-infected patients on suppressive antiretroviral therapy. The objective of this work was to evaluate the role of single nucleotide polymorphisms (SNPs) in lipopolysaccharide (LPS) Toll-like receptor 4 (TLR4) and CVDs occurrence in HIV-infected patients. Additionally, the functional consequences of carrying these SNPs were analyzed. Methods: The association of TLR4 SNPs, Asp299Gly/Thr399Ile with CVDs occurrence was analyzed using multivariate logistic regression models. Clinical, immunological, and traditional cardiovascular risk factors were used as covariates. The monocyte phenotype and response were assessed by multiparametric flow cytometry comparing carriers with noncarriers of this SNP. Results: Asp299Gly SNP, assayed in 253 HIV-infected patients, was independently associated with the occurrence of CVDs after adjusting for CD4(+) T-cell nadir, HCV-coinfection, bacterial pneumonia, diabetes mellitus, and traditional cardiovascular risk factors [odds ratio (confidence interval 95%) = 3.672 (1.061-12.712), P = 0.04). Carriers of Asp299Gly SNP showed higher percentage of patrolling and intermediate monocytes producing a proinflammatory combination of cytokines compared with noncarriers (P = 0.037 and P = 0.046, respectively). Intermediate monocyte subset levels correlated with soluble interleukin-6 levels only in carriers (r = 0.89; P = 0.01). Conclusion: TLR4 Asp299Gly polymorphism is independently associated with the occurrence of CVDs in HIV-infected patients. The proinflammatory profile associated to this variant could be involved in the development of atherosclerotic pathologies. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
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