Publication: Pharmacogenetics of cyclophosphamide and CYP2C19 polymorphism in Thai systemic lupus erythematosus
Issued Date
2011-09-01
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ISSN
1437160X
01728172
01728172
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2-s2.0-80054945119
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Mahidol University
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SCOPUS
Bibliographic Citation
Rheumatology International. Vol.31, No.9 (2011), 1215-1218
Suggested Citation
Pintip Ngamjanyaporn, Ammarin Thakkinstian, Oravan Verasertniyom, Porntip Chatchaipun, Monchand Vanichapuntu, Kanokrat Nantiruj, Kitti Totemchokchyakarn, John Attia, Suchela Janwityanujit Pharmacogenetics of cyclophosphamide and CYP2C19 polymorphism in Thai systemic lupus erythematosus. Rheumatology International. Vol.31, No.9 (2011), 1215-1218. doi:10.1007/s00296-010-1420-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/12001
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Title
Pharmacogenetics of cyclophosphamide and CYP2C19 polymorphism in Thai systemic lupus erythematosus
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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.