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Genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions in Thai population.
- Source :
-
Pharmacoepidemiology and drug safety [Pharmacoepidemiol Drug Saf] 2020 May; Vol. 29 (5), pp. 565-574. Date of Electronic Publication: 2020 Mar 05. - Publication Year :
- 2020
-
Abstract
- 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.<br />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.<br />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.<br />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.<br /> (© 2020 John Wiley & Sons Ltd.)
- Subjects :
- Case-Control Studies
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Retrospective Studies
Risk Factors
Sex Factors
Stevens-Johnson Syndrome etiology
Stevens-Johnson Syndrome genetics
Tertiary Care Centers
Thailand epidemiology
Anticonvulsants adverse effects
Phenytoin adverse effects
Stevens-Johnson Syndrome epidemiology
Subjects
Details
- Language :
- English
- ISSN :
- 1099-1557
- Volume :
- 29
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Pharmacoepidemiology and drug safety
- Publication Type :
- Academic Journal
- Accession number :
- 32134161
- Full Text :
- https://doi.org/10.1002/pds.4979