Prevalence and correlates of pharmacotherapy metabolized by CYP2C19, CYP2C9, CYP2D6, and UGT1A1 in the population sample

Objective: Telecommunication-based cross-sectional study aimed to assess prevalence and health-related correlates of pharmacogenetic (PGx) drug administration.

Methods: Online survey population sample (n = 2149) was initiated by SMS invitations to random adults. Questionnaire included questions on demographics, health, and clinical pharmacology. PGx drugs were identified using ClinPGx/PharmGKB database. Combined number of drug-gene interactions involving CYP2C19, CYP2C9, CYP2D6, and/or UGT1A1 was referred to as Z-score. Subgroup of respondents was genotyped for CYP2C19, CYP2C9, CYP2D6, and UGT1A1 variants.

Results: Nearly 70% of respondents were taking pharmacotherapy. Susceptibility to adverse drug reactions (ADRs) positively correlated with PGx drug intake (p = 0.03454, n = 2149). Susceptibility to ADRs in genotyped group (n = 83) correlated with carriership of loss-of-function variants of UGT1A1 (7TA/7TA, r = 0.2355, p = 0.03796), CYP2C19 (*2/*17, r = 0.3317, p = 0.003012), and combined carriership of loss-of-function variants of four study genes (r = 0.2291, p = 0.04361). One, two, and three actionable drug-gene interactions were present in 15.7%, 10.8%, and 1.2% of cases, respectively.

Conclusions: Carriership of loss-of-function variants of study pharmacogenes was associated with increased susceptibility of participants to ADRs. Further research is needed to elucidate clinical relevance of PGx burden at population level.

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