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Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders.
J Infect Dis. 2005 May 01; 191(9):1419-26.JI

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.

Authors+Show Affiliations

Infectious Diseases Service, University Hospital, Lausanne, Switzerland. philip.tarr@chuv.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15809899

Citation

Tarr, Philip E., et al. "Modeling the Influence of APOC3, APOE, and TNF Polymorphisms On the Risk of Antiretroviral Therapy-associated Lipid Disorders." The Journal of Infectious Diseases, vol. 191, no. 9, 2005, pp. 1419-26.
Tarr PE, Taffé P, Bleiber G, et al. Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders. J Infect Dis. 2005;191(9):1419-26.
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. (2005). Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders. The Journal of Infectious Diseases, 191(9), 1419-26.
Tarr PE, et al. Modeling the Influence of APOC3, APOE, and TNF Polymorphisms On the Risk of Antiretroviral Therapy-associated Lipid Disorders. J Infect Dis. 2005 May 1;191(9):1419-26. PubMed PMID: 15809899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders. AU - Tarr,Philip E, AU - Taffé,Patrick, AU - Bleiber,Gabriela, AU - Furrer,Hansjakob, AU - Rotger,Margalida, AU - Martinez,Raquel, AU - Hirschel,Bernard, AU - Battegay,Manuel, AU - Weber,Rainer, AU - Vernazza,Pietro, AU - Bernasconi,Enos, AU - Darioli,Roger, AU - Rickenbach,Martin, AU - Ledergerber,Bruno, AU - Telenti,Amalio, AU - ,, Y1 - 2005/03/22/ PY - 2004/07/26/received PY - 2004/11/08/accepted PY - 2005/4/6/pubmed PY - 2005/7/6/medline PY - 2005/4/6/entrez SP - 1419 EP - 26 JF - The Journal of infectious diseases JO - J Infect Dis VL - 191 IS - 9 N2 - 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. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/15809899/Modeling_the_influence_of_APOC3_APOE_and_TNF_polymorphisms_on_the_risk_of_antiretroviral_therapy_associated_lipid_disorders_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/429295 DB - PRIME DP - Unbound Medicine ER -