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Role of toll-like receptor 4 Asp299Gly polymorphism in the development of cardiovascular diseases in HIV-infected patients
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2018
-
Abstract
- [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.<br />[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.<br />[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).<br />[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.
- Subjects :
- 0301 basic medicine
Adult
Male
Immunology
Single-nucleotide polymorphism
HIV Infections
030204 cardiovascular system & hematology
Polymorphism, Single Nucleotide
Proinflammatory cytokine
03 medical and health sciences
0302 clinical medicine
Risk Factors
Diabetes mellitus
medicine
Immunology and Allergy
SNP
Humans
Genetic Predisposition to Disease
business.industry
Monocyte
Bacterial pneumonia
Odds ratio
medicine.disease
Toll-Like Receptor 4
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
Cardiovascular Diseases
TLR4
Female
business
Subjects
Details
- ISSN :
- 14735571
- Volume :
- 32
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- AIDS (London, England)
- Accession number :
- edsair.doi.dedup.....7ad40b2f64332fd26b74f6b189ca432f