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Title: Pharmacogenetics of cyclophosphamide and CYP2C19 polymorphism in Thai systemic lupus erythematosus
Authors: Pintip Ngamjanyaporn
Ammarin Thakkinstian
Oravan Verasertniyom
Porntip Chatchaipun
Monchand Vanichapuntu
Kanokrat Nantiruj
Kitti Totemchokchyakarn
John Attia
Suchela Janwityanujit
Mahidol University
University of Newcastle, Australia
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Sep-2011
Citation: Rheumatology International. Vol.31, No.9 (2011), 1215-1218
Abstract: To assess whether the CYP2C19 polymorphism modified the effect of cyclophosphamide on ovarian toxicity in Thai patients with SLE. We performed a case-control study of female patients with SLE who were treated with cyclophosphamide at Ramathibodi Hospital, Bangkok, Thailand. Cases were patient who had ovarian toxicity (sustained amenorrhoea > 12 months or lack of menstruation for > 4 months). CYP2C19 polymorphism was genotyped using PCR-RFLP method. Logistic regression was applied to assess CYP2C19 polymorphism as an effect modifier of cyclophosphamide. Seventy-one patients with SLE were enrolled, of which 36 (59.7%) had ovarian toxicity. CYP2C19*2 allele frequencies were 27.8 and 21.4% in the ovarian and non-ovarian toxicity groups. Patients with CYP2C19*1/*1 genotype and higher cumulative dose of cyclophosphamide ( > 23.75 g) had the highest odds of ovarian toxicity, i.e. 11.0 (95% CI: 1.2-99.1) times higher than patients with the CYP2C19*1/ *2 or*2/*2 genotypes who received less cyclophosphamide ( < 23.75 g). After adjusting for age at start of treatment, this risk increased to 13.6 (95% CI: 1.1-162.2). Our results suggest that a cumulative cyclophosphamide dose of 23.75 g or higher carries a twofold higher risk of ovarian toxicity and the CYP2C19*1/*1 genotype increases the risk of toxicity a further fivefold. © 2010 Springer-Verlag.
ISSN: 1437160X
Appears in Collections:Scopus 2011-2015

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