Genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions in Thai population.
Pharmacoepidemiol Drug Saf
; 29(5): 565-574, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32134161
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.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*4601 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*5602/04 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*4001 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*4601, CYP2C9*3, HLA-B*5602/04 and HLA-B*4001) 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenitoína
/
Síndrome de Stevens-Johnson
/
Anticonvulsivantes
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Pharmacoepidemiol Drug Saf
Asunto de la revista:
EPIDEMIOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Tailandia