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Rheumatology International

, Volume 31, Issue 9, pp 1215–1218 | Cite as

Pharmacogenetics of cyclophosphamide and CYP2C19 polymorphism in Thai systemic lupus erythematosus

  • Pintip NgamjanyapornEmail author
  • Ammarin ThakkinstianEmail author
  • Oravan Verasertniyom
  • Porntip Chatchaipun
  • Monchand Vanichapuntu
  • Kanokrat Nantiruj
  • Kitti Totemchokchyakarn
  • John Attia
  • Suchela Janwityanujit
Original Article

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.

Keywords

SLE (systemic lupus erythematosus) Cyclophosphamide CYP2C19 Ovarian toxicity Pharmacogenetics 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Pintip Ngamjanyaporn
    • 1
    Email author
  • Ammarin Thakkinstian
    • 2
    Email author
  • Oravan Verasertniyom
    • 3
  • Porntip Chatchaipun
    • 2
  • Monchand Vanichapuntu
    • 3
  • Kanokrat Nantiruj
    • 1
  • Kitti Totemchokchyakarn
    • 1
  • John Attia
    • 4
  • Suchela Janwityanujit
    • 1
  1. 1.Allergy Immunology and Rheumatology Division, Department of Medicine, Ramathibodi HospitalMahidol UniversityBangkokThailand
  2. 2.Section for Clinical Epidemiology and Biostatistics, Ramathibodi HospitalMahidol UniversityBangkokThailand
  3. 3.Research Center, Faculty of Medicine, Ramathibodi HospitalMahidol UniversityBangkokThailand
  4. 4.Centre for Clinical Epidemiology and BiostatisticsThe University of NewcastleNewcastleAustralia

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