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Title: | Polymorphisms of Pyrimidine Pathway Enzymes Encoding Genes and HLA-B*40∶01 Carriage in Stavudine-Associated Lipodystrophy in HIV-Infected Patients. |
Author: | Domingo, Pere (Domingo Pedrol) Mateo, Maria Gracia Pruvost, Alain Torres, Ferran Salazar, Juliana Gutiérrez, Maria del Mar Cabeza, María del Carmen Domingo i Pedrol, Joan Carles Fernández, Irene Villarroya i Gombau, Francesc Vidal, Francesc Baiget Bastús, Montserrat Calle Martín, Óscar de la |
Keywords: | Infeccions per VIH Medicaments Síndrome de lipodistròfia associada a VIH Enzimologia Genètica Polimorfisme genètic Metabolisme HIV infections Drugs HIV-associated lipodystrophy syndrome Enzymology Genetics Genetic polymorphisms Metabolism |
Issue Date: | 26-Jun-2013 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | Purpose To assess in a cohort of Caucasian patients exposed to stavudine (d4T) the association of polymorphisms in pyrimidine pathway enzymes and HLA-B*40∶01 carriage with HIV/Highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). Methods Three-hundred and thirty-six patients, 187 with HALS and 149 without HALS, and 72 uninfected subjects were recruited. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Polymorphisms in the thymidylate synthase (TS) and methylene-tetrahydrofolate reductase (MTHFR) genes were determined by direct sequencing, HLA-B genotyping by PCR-SSOr Luminex Technology, and intracellular levels of stavudine triphosphate (d4T-TP) by a LC-MS/MS assay method. Results HALS was associated with the presence of a low expression TS genotype polymorphism (64.7% vs. 42.9%, OR = 2.43; 95%CI: 1.53-3.88, P<0.0001). MTHFR gene polymorphisms and HLA-B*40∶01 carriage were not associated with HALS or d4T-TP intracellular levels. Low and high expression TS polymorphisms had different d4T-TP intracellular levels (25.60 vs. 13.60 fmol/106 cells, P<0.0001). Independent factors associated with HALS were(OR [95%CI]: (a) Combined TS and MTHFR genotypes (p = 0.006, reference category (ref.): 'A+A'; OR for 'A+B' vs. ref.: 1.39 [0.69-2.80]; OR for 'B+A' vs. ref.: 2.16 [1.22-3.83]; OR for 'B+B' vs. ref.: 3.13, 95%CI: 1.54-6.35), (b) maximum viral load ≥5 log10 (OR: 2.55, 95%CI: 1.56-4.14, P = 0.001), (c) use of EFV (1.10 [1.00-1.21], P = 0.008, per year of use). Conclusion HALS is associated with combined low-expression TS and MTHFR associated with high activity polymorphisms but not with HLA-B*40∶01 carriage in Caucasian patients with long-term exposure to stavudine. |
Note: | Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0067035 |
It is part of: | PLoS One, 2013, vol. 8, num. 6, p. 67035- |
URI: | http://hdl.handle.net/2445/127784 |
Related resource: | https://doi.org/10.1371/journal.pone.0067035 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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