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

Tarr, PE; 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; Swiss, HIV Cohort Study (2005). Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders. Journal of infectious diseases, 191(9), pp. 1419-26. Cary, N.C.: The University of Chicago Press 10.1086/429295

[img]
Preview
Text
191-9-1419.pdf - Published Version
Available under License Publisher holds Copyright.

Download (699kB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Furrer, Hansjakob

ISSN:

0022-1899

ISBN:

15809899

Publisher:

The University of Chicago Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:00

Last Modified:

27 Apr 2018 09:11

Publisher DOI:

10.1086/429295

PubMed ID:

15809899

Web of Science ID:

000228128800007

BORIS DOI:

10.7892/boris.25713

URI:

https://boris.unibe.ch/id/eprint/25713 (FactScience: 60789)

Actions (login required)

Edit item Edit item
Provide Feedback