Exploring the Correlation Between Genotypes of Drug-Metabolizing Enzymes and the Therapeutic Efficacy and Adverse Reactions of Cyclophosphamide in Childhood-Onset Lupus Nephritis: A Chinese Cohort Study.

OBJECTIVE

To investigate the association between genetic polymorphisms (CYP2B6, CYP2C19, GSTP1) and haplotypes of cyclophosphamide (CTX)-metabolizing enzymes with therapeutic efficacy and adverse drug reactions (ADRs) in pediatric patients with lupus nephritis (LN).

METHODS

A retrospective cohort study was conducted on 46 childhood-onset LN patients treated with CTX pulse therapy at Peking Union Medical College Hospital. Genetic polymorphisms of CYP2B6, CYP2C19, and GSTP1 were analyzed using blood samples. Patients were stratified into effective (n = 38) versus ineffective (n = 8) groups based on 3-month clinical outcomes, and adverse reaction (n = 13) versus control (n = 33) groups. Genotype/allele frequencies and haplotype distributions were compared using χ2 tests, Hardy-Weinberg equilibrium, and PHASE 2.1 software.

RESULTS

Mutations in CYP2C19 (rs4244285) and GSTP1 (rs1695) were associated with reduced therapeutic efficacy (p < 0.05). No significant differences in genotype/allele frequencies were observed between adverse reaction and control groups (p > 0.05). Haplotype distribution frequencies showed no association with ADRs and efficacy.

CONCLUSION

CYP2C19 × 2 and GSTP1 polymorphisms may reduce CTX efficacy in pediatric LN patients. Genetic variations showed no correlation with ADRs. These findings highlight the potential of pharmacogenetic testing to guide CTX therapy, though larger prospective studies are needed for validation.

CLINICAL TRIAL NUMBER: Not applicable.