Role of Cytochrome P450 Polymorphisms in the Development of Pulmonary Drug Toxicity A Case-Control Study in the Netherlands

Background: Drug-induced pulmonary toxicity is a serious and expanding problem with often unknown aetiology. Many drugs are metabolized by cytochrome P450 (CYP) enzymes. Objective: To establish whether allelic variation in CYP polymorphic genes contributes to variability in drug response and unexpected toxicity. Methods: A case-control study was conducted. The cases consisted of patients with drug-induced interstitial lung disease (DI-ILD; n = 59). Two control groups were used: one group of healthy volunteers (n = 173) and one group of patients with idiopathic pulmonary fibrosis (IPF; n = 110). Results: Of the patients with DI-ILD 91.5% (54/59) had at least one of the studied variant genes compared with 70.5% (122/173, p < 0.001) of the healthy volunteers and 69.1% (76/110, p < 0.001) of the IPF patients. The percentage of individuals with one or more variant CYP genes was higher in the DI-ILD group. Odds ratios were significantly increased and ranged from 3.25 to 40.8, indicating a significant association between the development of DI-ILD and the presence of one or more variant CYP genes. Conclusion: DI-ILD appeared to be associated with the presence of at least one variant CYP allele. This Study supports the potential usefulness of personalized medicine by genotyping aiming to improve efficacy, tolerability and drug safety.