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CYP2C19 genotype does not represent a genetic predisposition in idiopathic systemic lupus erythematosus
  1. Selim Kortunaya,
  2. Atila Bozkurta,
  3. Lise Bathumb,
  4. Nursabah E Bascia,
  5. Meral Çalgüneric,
  6. Kim Brøsend,
  7. S Oḡuz Kayaalpa
  1. aDepartment of Pharmacology, Faculty of Medicine, Hacettepe University, 06100, Ankara, Turkey, bDepartment of Clinical Chemistry, Odense University Hospital, Odense, Denmark, cDepartment of Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey, dDepartment of Clinical Pharmacology, Institute of Medical Biology, Odense University, Odense, Denmark
  1. Dr S Kortunay.

Abstract

BACKGROUND The aetiology of systemic lupus erythematosus (SLE) is still unknown. In several cases, however, chemicals or drugs were identified as aetiological agents and associations with certain phenotypes of drug metabolising enzymes have been reported. The purpose of this study was to discover if there is an association between CYP2C19 polymorphism and susceptibility to SLE.

METHODS Racemic mephenytoin (100 mg orally) was given to healthy volunteers (n=161) and SLE patients (n=37) and then S-mephenytoin and R-mephenytoin were determined in eight hour urine samples. A 10 ml blood sample was obtained from healthy volunteers (n=80) and SLE patients (n=69) for genotypic assay. Each blood sample was tested for the detection ofCYP2C19*1 andCYP2C19*2 (formerly wt and m1 respectively) by oligonucleotide ligation assay.

RESULTS The ratio of S/R-mephenytoin ranged from <0.1 to 1.293 in healthy subjects and from <0.1 to 1.067 in SLE patients. PM phenotype was observed in 2 of 37 patients with idiopathic SLE (5.4 %) and 6 of 161 healthy subjects (3.7 %). There were no significant differences in the frequency of PM phenotypes between the groups (Fisher’s exact test, p= 0.64) or in the frequency distribution profiles of ratios of S-mephenytoin to R-mephenytoin. No significant differences in distribution of overall genotypes and in allele frequencies were observed between the two groups. No significant relation was found between clinical features and the overall genotype.

CONCLUSION The results of this study indicate that CYP2C19 genotype does not represent a genetic predisposition in idiopathic SLE patients.

  • cytochrome P450
  • systemic lupus erythematosus
  • mephenytoine
  • genetic polymorphism

https://doi.org/10.1136/ard.58.3.182

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