CYP2C19 genotype does not represent a genetic predisposition in idiopathic systemic lupus erythematosus.
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 of CYP2C19*1 and CYP2C19*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.


CONCLUSIONS
The results of this study indicate that CYP2C19 genotype does not represent a genetic predisposition in idiopathic SLE patients.
Kortunay
S
S
Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Bozkurt
A
A
Bathum
L
L
Basci
N E
NE
Calgüneri
M
M
Brøsen
K
K
Kayaalp
S O
SO
D000328:Adult; D000927:Anticonvulsants / Q000652:urine; D001189:Aryl Hydrocarbon Hydroxylases; D016022:Case-Control Studies; D002849:Chromatography, Gas; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007536:Isomerism; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008617:Mephenytoin / Q000652:urine; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic
D000927:Anticonvulsants; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D008617:Mephenytoin