CYP2D6 polymorphism in systemic lupus erythematosus patients

Objectives: To determine whether patients with idiopathic systemic lupus er ythematosus (SLE) are associated with impaired CYP2D6 activity and to gain insight into whether there is an association between particular CYP2D6 geno types and susceptibility to SLE, and whether CYP2D6 polymorphism is linked to any specific clinical features of SLE. Methods: Debrisoquine sulfate (10 mg p.o.) was given to 159 healthy volunte ers and 39 idiopathic SLE patients. Genotypic assay was carried out in 80 h ealthy volunteers and 32 patients. A 10-ml blood sample was drawn for genot ypic assay. Debrisoquine and 4-hydroxydebrisoquine were determined in 8-h u rine samples. Blood samples were analysed for the presence of mutations in the CYP2D6 gene, by using polymerase chain reaction (PCR) specific for CYP2 D6*3 and CYP2D6*4 alleles. Results: The metabolic ratio of debrisoquine to 4-hydroxydebrisoquine range d from 0.01 to 86.98 in healthy subjects and from 0.02 to 96 in SLE patient s. We observed the poor metabolizer(Phl) debrisoquine phenotype in three of 39 patients with idiopathic SLE (7.6%) and five of 159 healthy subjects (3 .1%). There was no significant difference in the frequency of PM phenotypes between idiopathic SLE and healthy subjects (Fisher's exact test, P = 0.19 ). No significant difference in the distribution of overall genotypes and a llele frequencies were observed between the two groups. No significant rela tionships were found between specific clinical features and the overall gen otype. Conclusion: The results of this study confirm that CYP2D6 activity is not i mpaired in SLE and that there is no association between SLE and phenotypic CYP2D6 status. The results also showed that there was no difference in the frequency of CYP2D6A and CYP2D6B alleles between controls and patients with SLE.