RT Journal Article
T1 Role of toll-like receptor 4 Asp299Gly polymorphism in the development of cardiovascular diseases in HIV-infected patients.
A1 Tarancon-Diez, Laura
A1 De Pablo-Bernal, Rebeca S
A1 Jimenez, Jose L
A1 Alvarez-Rios, Ana I
A1 Genebat, Miguel
A1 Rosado-Sanchez, Isaac
A1 Muñoz-Fernandez, Maria-Angeles
A1 Ruiz-Mateos, Ezequiel
A1 Leal, Manuel
K1 Cardiovascular Diseases
K1 HIV Infections
K1 Male
K1 Toll-Like Receptor 4
AB 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. 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. 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). 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.
PB Lippincott Williams & Wilkins
YR 2018
FD 2018-05-15
LK http://hdl.handle.net/10668/12246
UL http://hdl.handle.net/10668/12246
LA en
NO Tarancon-Diez L, De Pablo-Bernal RS, Jiménez JL, Álvarez-Ríos AI, Genebat M, Rosado-Sánchez I, et al. Role of toll-like receptor 4 Asp299Gly polymorphism in the development of cardiovascular diseases in HIV-infected patients. AIDS. 2018 May 15;32(8):1035-1041.
DS RISalud
RD Apr 5, 2025