Genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions in Thai population.

Pharmacoepidemiology and Drug Safety
Chonlaphat SukasemSuvatna Chulavatnatol

Abstract

This study aimed to describe the genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions (PHT-induced cADRs) in Thai patients. A retrospective case-control study was conducted among 88 PHT- cADRs (25 SJS/TEN, 37 DRESS/DIHS and 26 MPE) compared to 70 PHT-tolerant controls during 2008-2017. Genotyping was performed by Taqman RT-PCR (EPHX1 337 T > C, EPHX1 416A > G and CYP2C9*3), pyrosequencing (UGT1A1*28, UGT1A1*6) and polymerase chain reaction-sequence-specific oligonucleotide probe (HLA-B). Chi-squared test and binary logistic regression were used to identify factors associated with PHT-cADRs. Multivariate analysis showed that HLA-B*46:01 was significantly associated with all PHT-induced cADRs (OR 2.341; 95% CI, 1.078-5.084; P = .032). Age of ≥60 years showed a significant association with PHT-induced SJS/TEN (OR 3.600; 95% CI, 1.214-10.672; P = .021). CYP2C9*3 was almost reaching statistically associated with an increased risk of PHT-induced SJS/TEN (OR 4.800; 95% CI, 0.960-23.990; P = .056). While HLA-B*56:02/04 was found to have a significant association with PHT-induced DRESS/DIHS (OR 29.312; 95% CI, 1.213-707.994; P = .038). Moreover, female gender and HLA-B*40:01 were associate...Continue Reading

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Citations

Jun 9, 2020·Expert Opinion on Drug Metabolism & Toxicology·Wan-Chun ChangWen-Hung Chung
Jun 10, 2021·Clinical and Translational Science·Chiara JeizinerHenriette E Meyer Zu Schwabedissen
Jun 22, 2021·Expert Opinion on Drug Metabolism & Toxicology·Thawinee JantararoungtongChonlaphat Sukasem

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