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Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis
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- Kindmark, Andreas (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Metabolic Bone Diseases
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Jawaid, A (författare)
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Harbron, C G (författare)
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Barratt, B J (författare)
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Bengtsson, O F (författare)
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- Andersson, T B (författare)
- Karolinska Institutet
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Carlsson, S (författare)
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Cederbrant, K E (författare)
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Gibson, N J (författare)
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Armstrong, M (författare)
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Lagerström-Fermér, M E (författare)
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Dellsén, A (författare)
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Brown, E M (författare)
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Thornton, M (författare)
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Dukes, C (författare)
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Jenkins, S C (författare)
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Firth, M A (författare)
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Harrod, G O (författare)
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Pinel, T H (författare)
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Billing-Clason, S M E (författare)
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Cardon, L R (författare)
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March, R E (författare)
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(creator_code:org_t)
- 2007-05-15
- Engelska.
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Ingår i: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 8:3, s. 186-195
- Relaterad länk:
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http://www.ncbi.nlm....
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- pharmacogenetics
- pharmacogenomics
- adverse event
- immune system
- liver injury
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)