Genetic polymorphism of CYP2D6 in patients with systemic lupus erythematosus and systemic sclerosis

Human organism is constantly exposed to harmful exogenous factors (xenobiotics) including drugs and carcinogenic compounds that can induce development of a large number of diseases. The processes of biotransformation in the organism are multidirectional and xenobiotics can be transformed into active or inactive metabolites via the oxidative route. The knowledge of oxidation polymorphism in the course of systemic lupus erythematosus and systemic sclerosis may be helpful in choosing more efficient and safer therapy, particularly in the case of a disease involving various organs and treated with drugs belonging to diverse therapeutic groups. The aim of the study was to evaluate the CYP2D6 polymorphism in the SLE (systemic lupus erythematosus) and SSc (systemic sclerosis) patients and to investigate a possible correlation with disease susceptibility. The study was carried out in 296 patients: 65 patients with SLE, 81 patients with SSc, and 150 healthy volunteers. The CYP2D6 genotypes were analyzed by polymerase chain reaction fragment length polymorphism (PCR-RFLP) method. The relative risk of developing SSc, expressed by the odds ratio, was three-fold higher for persons with the CYP2D6*1/CYP2D6*4 genotype (OR = 2.9; statistically significant difference, p = 0.0002). A statistically significant correlation between the CYP2D6*4 allele prevalence and the risk for developing SSc was found (OR = 1.53; p = 0.047). No effect of the CYP2D6 gene mutations on the incidence of SLE was noted. The obtained results may suggest the influence of CYP2D6*4 gene variants alleles on increased incidence of systemic sclerosis.