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- Title
Modeling the Influence of APOC3, APOE, and TNF Polymorphisms on the Risk of Antiretroviral Therapy-Associated Lipid Disorders.
- Authors
Tarr, Philip E.; Taffé, Patrick; Bleiber, Gabriela; Furrer, Hansjakob; Rotger, Margalida; Martinez, Raquel; Hirschel, Bernard; Battegay, Manuel; Weber, Rainer; Vernazza, Pietro; Bernasconi, Enos; Darioli, Roger; Rickenbach, Martin; Ledergerber, Bruno; Telenti, Amalio
- 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 APOG3 -482C → T, -455T→C, and 3238C→G; ϵ2 and ϵ4 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 APOG3 on plasma triglyceride levels were comparable to those reported in the general population. However, when treated with ritonavir, individuals with unfavorable genotypes of APOG3 or APOE were at risk of extreme hypertriglyceridemia. They had me than 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*APOG3*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 APOG3 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.
- Subjects
ANTIVIRAL agents; TRIGLYCERIDES; HIV; GENETIC polymorphisms; HYPERTRIGLYCERIDEMIA; ISOPENTENOIDS
- Publication
Journal of Infectious Diseases, 2005, Vol 191, Issue 9, p1419
- ISSN
0022-1899
- Publication type
Article