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2013-06-26

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cc-by (c) Domingo, Pere (Domingo Pedrol) et al., 2013
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/127784

Polymorphisms of Pyrimidine Pathway Enzymes Encoding Genes and HLA-B*40∶01 Carriage in Stavudine-Associated Lipodystrophy in HIV-Infected Patients.

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https://doi.org/10.1371/journal.pone.0067035

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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.

Matèries

Infeccions per VIH, Medicaments, Síndrome de lipodistròfia associada a VIH, Enzimologia, Genètica, Polimorfisme genètic, Metabolisme

Matèries (anglès)

HIV infections, Drugs, HIV-associated lipodystrophy syndrome, Enzymology, Genetics, Genetic polymorphisms, Metabolism

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

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 MARSAL, Francisco, BAIGET BASTÚS, Montserrat, CALLE MARTÍN, Óscar de la. Polymorphisms of Pyrimidine Pathway Enzymes Encoding Genes and HLA-B*40∶01 Carriage in Stavudine-Associated Lipodystrophy in HIV-Infected Patients.. _PLoS One_. 2013. Vol. 8, núm. 6, pàgs. 67035-. [consulta: 20 de gener de 2026]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/127784]

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