Pharmacogenetics of methotrexate in patients with rheumatoid
arthritis
Wessels, J.A.M
Citation
Wessels, J. A. M. (2007, October 11). Pharmacogenetics of methotrexate in patients with
rheumatoid arthritis. Retrieved from https://hdl.handle.net/1887/12436
Version: Corrected Publisher’s Version
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Pharmacogenetics of Methotrexate in
Patients with Rheumatoid Arthritis
Judith Wessels
Pharmacogenetics of Methotrexate in
Patients with Rheumatoid Arthritis
Proefschrift
ter verkrijging van de graad van
Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus
prof. mr. P.F. van der Heijden,
volgens besluit van
het College voor Promoties
te verdedigen op 11 oktober 2007
klokke 16.15 uur door
Judith Anne-Marie Wessels
geboren te Lichtenvoorde
in 1974
promotores Prof. Dr. H.-J. Guchelaar Prof. Dr. T.W.J. Huizinga
referent Prof. Dr. B.N. Cronstein
New York University School of Medicine, New York
overige leden Prof. Dr. A.C.G. Egberts
Universiteit Utrecht Prof. Dr. P. de Knijff
Prof. Dr. G.J.B. van Ommen Prof. Dr. P.L.C.M. van Riel Universiteit Nijmegen
The research presented in this thesis was performed at the Department of Clinical Pharmacy and Toxicology and at the Rheumatology Department of Leiden University Medical Centre, Leiden, The Netherlands. The research was financially supported by the Foundations Nuts Ohra (Amsterdam) and ‘De Drie Lichten’ (Leiden), The Netherlands.
© Judith Wessels, 2007. Except: Chapter 4, 5 and 7: Reproduced from Arthritis and Rheumatism, Wessels et al., pages 1087–1095 and 2830–2839 (2006) and pages 1765–1775 (2007), John Wiley & Sons Inc.; Chapter 3: Reproduced from Current Rheumatology Reports, Wesoly et al., edition 8 (2006), Philadelphia, Current Medicine Group LLC;
Chapter 6: Reproduced from Pharmacogenomics, van der Straaten et al., edition 8, pages 141–150 (2007), Future Medicine Ltd; with permission.
Niets uit deze uitgave mag worden verveelvoudigd en/of openbaar gemaakt zonder voorafgaande schriftelijke toestemming van de auteur. No Part of this thesis may be reproduced in any form without written permission from the author.
isbn 978-90-9022114-4
Foto omslag Joost van den Broek, Hollandse Hoogte
Gedicht Zuiverheid, from: De encyclopedie van de grote woorden (2005), Mark Boog;
with kind permission of the author.
Vormgeving Sam Gobin, Leiden
Druk Drukkerij Mostert & Van Onderen, Leiden
The printing of this thesis was financially supported by AZL Onderzoeks- en Ontwikkelingskrediet Apotheek, Dutch Arthritis Association, ABBOTT B.V., Interpharm B.V., Dr. Ir. J.E Jurriaanse Stichting, Stichting KNMP Fondsen, OPG Distrimed B.V., Pfizer B.V., Roche Pharmaceuticals B.V., Schering-Plough, Wyeth Pharmaceuticals B.V., Bristol- Meyers-Squibb B.V., Amgen B.V. (Breda), Centocor B.V., AstraZeneca B.V.
Aan mijn ouders
1 General introduction – 7
2 Recent insights in the pharmacologic actions of methotrexate in the treatment of rheumatoid arthritis patients – 13
3 Genetic markers of treatment response in rheumatoid arthritis – 29
4 Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes –43
5 Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent- onset rheumatoid arthritis – 59
6 Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients – 73
7 A clinical pharmacogenetic model to predict the efficacy of meth- otrexate monotherapy in recent-onset rheumatoid arthritis – 85
8 Genome-wide analysis of rheumatoid arthritis patients for single nucleotide polymorphisms associated with methotrexate induced liver injury – 101
9 Summary – Pharmacogenetics of methotrexate in patients with rheumatoid arthritis – 113
10 General discussion and conclusion – Pharmacogenetics of inflammatory arthritis – 117
Role of the funding source, acknowledgements – 135 Nederlandse samenvatting – 137Nederlandse samenvatting – 137 – 137
List of publications – 142 Curriculum Vitae – 143 Nawoord – 144
