Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders.

Details

Ressource 1Download: serval:BIB_811D1E662350.P001 (683.51 [Ko])
State: Public
Version: author
License: Not specified
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_811D1E662350
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders.
Journal
Journal of Infectious Diseases
Author(s)
Tarr P.E., Taffé P., Bleiber G., Furrer H., Rotger M., Martinez R., Hirschel B., Battegay M., Weber R., Vernazza P., Bernasconi E., Darioli R., Rickenbach M., Ledergerber B., Telenti A.
ISSN
0022-1899
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
191
Number
9
Pages
1419-1426
Language
english
Notes
Journal Article Multicenter Study Research Support, Non-U.S. Gov't --- Old month value: May 1
Abstract
BACKGROUND: Single-nucleotide polymorphisms in genes involved in lipoprotein and adipocyte metabolism may explain why dyslipidemia and lipoatrophy occur in some but not all antiretroviral therapy (ART)-treated individuals. METHODS: We evaluated the contribution of APOC3 -482C-->T, -455T-->C, and 3238C-->G; epsilon 2 and epsilon 4 alleles of APOE; and TNF -238G-->A to dyslipidemia and lipoatrophy by longitudinally modeling >2600 lipid determinations and 2328 lipoatrophy assessments in 329 ART-treated patients during a median follow-up period of 3.4 years. RESULTS: In human immunodeficiency virus (HIV)-infected individuals, the effects of variant alleles of APOE on plasma cholesterol and triglyceride levels and of APOC3 on plasma triglyceride levels were comparable to those reported in the general population. However, when treated with ritonavir, individuals with unfavorable genotypes of APOC3 and [corrected] APOE were at risk of extreme hypertriglyceridemia. They had median plasma triglyceride levels of 7.33 mmol/L, compared with 3.08 mmol/L in the absence of ART. The net effect of the APOE*APOC3*ritonavir interaction was an increase in plasma triglyceride levels of 2.23 mmol/L. No association between TNF -238G-->A and lipoatrophy was observed. CONCLUSIONS: Variant alleles of APOE and APOC3 contribute to an unfavorable lipid profile in patients with HIV. Interactions between genotypes and ART can lead to severe hyperlipidemia. Genetic analysis may identify patients at high risk for severe ritonavir-associated hypertriglyceridemia.
Keywords
Alleles, Anti-HIV Agents, Apolipoprotein C-III, Apolipoproteins C, Apolipoproteins E, CD4 Lymphocyte Count, Cohort Studies, Female, Genetic Variation, HIV Infections, Humans, Hypertriglyceridemia, Male, Middle Aged, Multivariate Analysis, Polymorphism, Single Nucleotide, Risk Assessment, Switzerland, Tumor Necrosis Factor-alpha
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 12:45
Last modification date
25/09/2019 7:09
Usage data