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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 (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Metabolic Bone Diseases
- Jawaid, A (author)
- Harbron, C G (author)
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- Barratt, B J (author)
- Bengtsson, O F (author)
- Carlsson, S (author)
- Cederbrant, K E (author)
- Gibson, N J (author)
- Armstrong, M (author)
- Lagerström-Fermér, M E (author)
- Dellsén, A (author)
- Brown, E M (author)
- Thornton, M (author)
- Dukes, C (author)
- Jenkins, S C (author)
- Firth, M A (author)
- Harrod, G O (author)
- Pinel, T H (author)
- Billing-Clason, S M E (author)
- Cardon, L R (author)
- March, R E (author)
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- (creator_code:org_t)
- 2007-05-15
- 2008
- English.
- In: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 8:3, s. 186-195
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Keyword
- pharmacogenetics
- pharmacogenomics
- adverse event
- immune system
- liver injury
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Jawaid, A
- Harbron, C G
- Barratt, B J
- Bengtsson, O F
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- Carlsson, S
- Cederbrant, K E
- Gibson, N J
- Armstrong, M
- Lagerström-Fermé ...
- Dellsén, A
- Brown, E M
- Thornton, M
- Dukes, C
- Jenkins, S C
- Firth, M A
- Harrod, G O
- Pinel, T H
- Billing-Clason, ...
- Cardon, L R
- March, R E
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