Modeling the Influence of APOC3, APOE and TNF Polymorphisms on the Risk of Antiretroviral Therapy-Associated Lipid Disorders

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

In: The Journal of Infectious Diseases, 2005, vol. 191, no. 9, p. 1419-1426

Aggiungi alla tua lista
    BackgroundSingle-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 MethodsWe evaluated the contribution of APOC3 −482C→T, −455T→C, and 3238C→G; ɛ2 and ɛ4 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 ResultsIn 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 or 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 ConclusionsVariant 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