1. Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis.
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Kindmark, A., Jawaid, A., Harbron, C. G., Barratt, B. J., Bengtsson, O. F., Andersson, T. B., Carlsson, S., Cederbrant, K. E., Gibson, N. J., Armstrong, M, Lagerström-Fermér, M. E., Dellsén, A., Brown, E. M., Thornton, M., Dukes, C., Jenkins, S. C., Firth, M. A., Harrod, G. O., Pinel, T. H., and Billing-Clason, S. M. E
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PHARMACOGENOMICS ,LIFE change events ,ALANINE ,AMINOTRANSFERASES ,NUCLEOTIDES - Abstract
One of the major goals of pharmacogenetics is to elucidate mechanisms and identify patients at increased risk of adverse events (AEs). To date, however, there have been only a few successful examples of this type of approach. In this paper, we describe a retrospective case–control pharmacogenetic study of an AE of unknown mechanism, characterized by elevated levels of serum alanine aminotransferase (ALAT) during long-term treatment with the oral direct thrombin inhibitor ximelagatran. The study was based on 74 cases and 130 treated controls and included both a genome-wide tag single nucleotide polymorphism and large-scale candidate gene analysis. A strong genetic association between elevated ALAT and the MHC alleles DRB1
* 07 and DQA1* 02 was discovered and replicated, suggesting a possible immune pathogenesis. Consistent with this hypothesis, immunological studies suggest that ximelagatran may have the ability to act as a contact sensitizer, and hence be able to stimulate an adaptive immune response.The Pharmacogenomics Journal (2008) 8, 186–195; doi:10.1038/sj.tpj.6500458; published online 15 May 2007 [ABSTRACT FROM AUTHOR]- Published
- 2008
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