Publication: Genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions in Thai population
Issued Date
2020-01-01
Resource Type
ISSN
10991557
10538569
10538569
DOI
Other identifier(s)
2-s2.0-85080930244
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Pharmacoepidemiology and Drug Safety. (2020)
Suggested Citation
Chonlaphat Sukasem, Suthida Sririttha, Therdpong Tempark, Jettanong Klaewsongkram, Ticha Rerkpattanapipat, Apichaya Puangpetch, Apisit Boongird, Suvatna Chulavatnatol Genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions in Thai population. Pharmacoepidemiology and Drug Safety. (2020). doi:10.1002/pds.4979 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/53839
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions in Thai population
Abstract
© 2020 John Wiley & Sons Ltd Objective: 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. Method: 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. Results: 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 associated with an increased risk of PHT-induced MPE at OR 5.734; 95% CI, 0.910-58.351; P =.042 and OR 3.647; 95% CI, 1.193-11.147; P =.023, respectively. Conclusion: Both clinical (advanced age, female gender) and genetic factors (HLA-B*46:01, CYP2C9*3, HLA-B*56:02/04 and HLA-B*40:01) contributed to the risk of PHT-induced cADRs. Further studies with larger sample size may be warranted to confirm these findings and also the influence of EPHX1 gene.