2024-03-28T13:17:07Zhttps://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/85772021-06-23T09:48:50Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
UVaDOC
author
Lucena, M. Isabel
author
Molokhia, Mariam
author
Shen, Yufeng
author
Urban, Thomas J.
author
Aithad, Guruprasad P.
author
Andrade, Raúl J
author
Day, Christopher P.
author
Ruiz Cabello, Francisco
author
Donaldson, Peter T.
author
Stephens, Camilla
author
Pirmohamed, Munir
author
Romero Gómez, Manuel
author
Navarro, José María
author
Fontana, Roberto J.
author
Miller, Michael
author
Groome, Max
author
Bondon-Guitton, Emmanuelle
author
Conforti, Anita
author
Stricker, Bruno H.C.
author
Carvajal García-Pando, Alfonso
author
Ibánez, Luisa
author
Yue, Qun-Ying
author
Eichelbaum, Michel
author
Floratos, Aris
author
Pe’er, Itsik
author
Daly, Mark J.
author
Goldstein, David B.
author
Dillon, John F.
author
Nelson, Matthew R.
author
Watkins, Paul B.
author
Daly, Ann K.
2015-03-02T13:04:12Z
2015-03-02T13:04:12Z
2011
Gastroenterology. 2011 Jul; 141(1): 338–347
0016-5085
http://uvadoc.uva.es/handle/10324/8577
10.1053/j.gastro.2011.04.001
338
1
347
Gastroenterology
141
Background & Aims
Drug-induced liver injury (DILI), especially from antimicrobial agents, is an important cause of serious liver disease. Amoxicillin-clavulanate (AC) is a leading cause of idiosyncratic DILI, but little is understood about genetic susceptibility to this adverse reaction.
Methods
We performed a genome-wide association study using 822,927 single-nucleotide polymorphism (SNP) markers from 201 White European and US cases of AC-DILI and 532 population controls, matched for genetic background.
Results
AC-DILI was associated with many loci in the major histocompatibility complex. The strongest effect was with a human leukocyte antigen (HLA) class II SNP (rs9274407, P=4.8×10−14), which correlated with rs3135388, a tag SNP of HLA-DRB1*1501-DQB1*0602 that was previously associated with AC-DILI. Conditioned on rs3135388, rs9274407 is still significant (P=1.1×10−4). An independent association was observed in the class I region (rs2523822, P=1.8×10−10), related to HLA-A*0201. The most significant class I and II SNPs showed statistical interaction (P=0.0015). High-resolution HLA genotyping (177 cases and 219 controls) confirmed associations of HLA-A*0201 (P=2×10−6) and HLA-DQB1*0602 (P=5×10−10), and their interaction (P=0.005). Additional, population-dependent effects were observed in HLA alleles with nominal significance. In an analysis of auto-immunerelated genes, rs2476601 in the gene PTPN22 was associated (P=1.3×10−4).
Conclusions
Class I and II HLA genotypes affect susceptibility to AC-DILI, indicating the importance of the adaptive immune response in pathogenesis. The HLA genotypes identified will be useful in studies of the pathogenesis of AC-DILI, but have limited utility as predictive or diagnostic biomarkers because of the low positive-predictive values.
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
Amoxicilina - Efectos secundarios
Susceptibility to Amoxicillin-Clavulanate-Induced Liver Injury Is Influenced by Multiple HLA Class I and II Alleles
info:eu-repo/semantics/article
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
URL
https://uvadoc.uva.es/bitstream/10324/8577/1/Carvajal%201-PD%20204.pdf
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application/pdf
Carvajal 1-PD 204.pdf