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CYP2C19 genotype does not represent a genetic predisposition in
idiopathic systemic lupus erythematosus
uz Kayaalpa
a Department of
Pharmacology, Faculty of Medicine, Hacettepe University, 06100, Ankara,
Turkey, b Department of Clinical
Chemistry, Odense University Hospital, Odense, Denmark, c Department of Rheumatology, Faculty of Medicine,
Hacettepe University, Ankara, Turkey, d Department
of Clinical Pharmacology, Institute of Medical Biology, Odense
University, Odense, Denmark
Correspondence to: Dr S Kortunay.
Accepted for publication 25 November 1998
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.
METHODSRacemic
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 of
CYP2C19*1 and
CYP2C19*2 (formerly wt and m1 respectively)
by oligonucleotide ligation assay.
RESULTSThe
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.
CONCLUSIONThe results
of this study indicate that CYP2C19 genotype
does not represent a genetic predisposition in idiopathic SLE patients.
© 1999 by Annals of the Rheumatic Diseases
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