Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/58285
Title: Association of thymidylate synthase polymorphisms with acute pancreatitis and/or peripheral neuropathy in HIV-infected patients on Stavudine-Based Therapy
Author: Domingo, Pere (Domingo Pedrol)
Cabeza, María del Carmen
Torres, Ferran
Salazar, Juliana
Gutiérrez, Maria del Mar
Mateo, Maria Gracia
Martínez Chamorro, Esteban José
Domingo i Pedrol, Joan Carles
Fernández, Irene
Villarroya i Gombau, Francesc
Ribera, Esteban
Vidal, Francesc
Baiget, Montserrat
Keywords: Infeccions per VIH
Malalties del sistema nerviós
Pancreatitis
Assaigs clínics
HIV infections
Nervous System Diseases
Pancreatitis
Clinical trials
Issue Date: 28-Feb-2013
Publisher: Public Library of Science (PLoS)
Abstract: BACKGROUND: Low expression thymidylate synthase (TS) polymorphism has been associated with increased stavudine triphosphate intracellular (d4T-TP) levels and the lipodystrophy syndrome. The use of d4T has been associated with acute pancreatitis and peripheral neuropathy. However, no relationship has ever been proved between TS polymorphisms and pancreatitis and/or peripheral neuropathy. METHODS: We performed a case-control study to assess the relationship of TS and methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms with acute pancreatitis and/or peripheral neuropathy in patients exposed to d4T. Student's t test, Pearson's correlations, one-way ANOVA with Bonferroni correction and stepwise logistic regression analyses were done. RESULTS: Forty-three cases and 129 controls were studied. Eight patients (18.6%) had acute pancreatitis, and 35 (81.4%) had peripheral neuropathy. Prior AIDS was more frequent in cases than in controls (OR = 2.36; 95%CI 1.10-5.07, P = 0.0247). L7ow expression TS and MTHFR genotype associated with increased activity were more frequent in patients with acute pancreatitis and/or peripheral neuropathy than in controls (72.1% vs. 46.5%, OR = 2.97; 95%CI: 1.33-6.90, P = 0.0062, and 79.1% vs. 56.6%, OR = 2.90, 95%CI: 1.23-7.41, P = 0.0142, respectively). Independent positive or negative predictors for the development of d4T-associated pancreatitis and/or peripheral neuropathy were: combined TS and MTHFR genotypes (reference: A+A; P = 0.002; ORA+B = 0.34 [95%CI: 0.08 to 1.44], ORB+A = 3.38 [95%CI: 1.33 to 8.57], ORB+B = 1.13 [95%CI: 0.34 to 3.71]), nadir CD4 cell count >200 cells/mm(3) (OR = 0.38; 95%CI: 0.17-0.86, P = 0.021), and HALS (OR = 0.39 95%CI: 0.18-0.85, P = 0.018). CONCLUSIONS: Low expression TS plus a MTHFR genotype associated with increased activity is associated with the development of peripheral neuropathy in d4T-exposed patients.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0057347
It is part of: PLoS One, 2013, vol. 8, num. 2, p. e57347
Related resource: http://dx.doi.org/10.1371/journal.pone.0057347
URI: http://hdl.handle.net/2445/58285
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Medicina)

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