- Title
- Pharmacogenetics of cyclophosphamide and CYP2C19 polymorphism in Thai systemic lupus erythematosus
- Creator
- Ngamjanyaporn, Pintip; Thakkinstian, Ammarin; Verasertniyom, Oravan; Chatchaipun, Porntip; Vanichapuntu, Monchand; Nantiruj, Kanokrat; Totemchokchyakarn, Kitti; Attia, John; Janwityanujit, Suchela
- Relation
- Rheumatology International Vol. 31, Issue 9, p. 1215-1218
- Publisher Link
- http://dx.doi.org/10.1007/s00296-010-1420-7
- Publisher
- Springer
- Resource Type
- journal article
- Date
- 2011
- Description
- 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.
- Subject
- SLE (systemic lupus erythematosus); cyclophosphamide; CYP2C19; ovarian toxicity; pharmacogenetics
- Identifier
- http://hdl.handle.net/1959.13/937045
- Identifier
- uon:12479
- Identifier
- ISSN:0172-8172
- Language
- eng
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