CYP2C19 genotype does not represent a genetic predisposition in idiopathicsystemic lupus erythematosus

Background-The aetiology of systemic lupus erythematosus (SLE) is still unk nown. In several cases, however, chemicals or drugs were identified as aeti ological agents and associations with certain phenotypes of drug metabolisi ng 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 w ere determined in eight hour urine samples. A 10 ml blood sample was obtain ed from healthy volunteers (n=80) and SLE patients (n=69) for genotypic ass ay. Each blood sample was tested for the detection of CYP2C19*1 and CYP2C19 *2 (formerly wt and mi respectively) by oligonucleotide ligation assay. Results-The ratio of SIR-mephenytoin ranged from <0.1 to 1.293 in healthy s ubjects and from <0.1 to 1.067 in SLE patients. FM phenotype was observed i n 2 of 37 patients with idiopathic SLE (5.4 %) and 6 of 161 healthy subject s (3.7 %). There were no significant differences in the frequency of PM phe notypes between the groups (Fisher's exact test, p= 0.64) or in the frequen cy distribution profiles of ratios of S-mephenytoin to R-mephenytoin. No si gnificant differences in distribution of overall genotypes and in allele fr equencies 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 no t represent a genetic predisposition in idiopathic SLE patients.