PMID- 34442381
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210831
IS  - 2075-4426 (Print)
IS  - 2075-4426 (Electronic)
IS  - 2075-4426 (Linking)
VI  - 11
IP  - 8
DP  - 2021 Jul 28
TI  - Association of HLA-B*51:01, HLA-B*55:01, CYP2C9*3, and Phenytoin-Induced 
      Cutaneous Adverse Drug Reactions in the South Indian Tamil Population.
LID - 10.3390/jpm11080737 [doi]
LID - 737
AB  - Phenytoin (PHT) is one of the most commonly reported aromatic anti-epileptic 
      drugs (AEDs) to cause cutaneous adverse reactions (CADRs), particularly severe 
      cutaneous adverse reactions (SCARs). Although human leukocyte antigen 
      (HLA)-B*15:02 is associated with PHT-induced Steven Johnson syndrome/toxic 
      epidermal necrosis (SJS/TEN) in East Asians, the association is much weaker than 
      it is reported for carbamazepine (CBZ). In this study, we investigated the 
      association of pharmacogenetic variants of the HLA B gene and CYP2C9*3 with 
      PHT-CADRs in South Indian epileptic patients. This prospective case-controlled 
      study included 25 PHT-induced CADRs, 30 phenytoin-tolerant patients, and 463 
      (HLA-B) and 82 (CYP2C9*3) normal-controls from previous studies included for the 
      case and normal-control comparison. Six SCARs cases and 19 mild-moderate 
      reactions were observed among the 25 cases. Pooled data analysis was performed 
      for the HLA B*51:01 and PHT-CADRs associations. The Fisher exact test and 
      multivariate binary logistic regression analysis were used to identify the 
      susceptible alleles associated with PHT-CADRs. Multivariate analysis showed that 
      CYP2C9*3 was significantly associated with overall PHT-CADRs (OR = 12.00, 95% CI 
      2.759-84.87, p = 003). In subgroup analysis, CYP2C9*3 and HLA B*55:01 were found 
      to be associated with PHT-SCARs (OR = 12.45, 95% CI 1.138-136.2, p = 0.003) and 
      PHT-maculopapular exanthema (MPE) (OR = 4.041, 95% CI 1.125-15.67, p = 0.035), 
      respectively. Pooled data analysis has confirmed the association between HLA 
      B*51:01/PHT-SCARs (OR = 6.273, 95% CI 2.24-16.69, p = <0.001) and HLA 
      B*51:01/PHT-overall CADRs (OR = 2.323, 95% CI 1.22-5.899, p = 0.037). In this 
      study, neither the case nor the control groups had any patients with HLA B*15:02. 
      The risk variables for PHT-SCARs, PHT-overall CADRs, and PHT-MPE were found to be 
      HLA B*51:01, CYP2C9*3, and HLA B*55:01, respectively. These alleles were 
      identified as the risk factors for the first time in the South Indian Tamil 
      population for PHT-CADRs. Further investigation is warranted to establish the 
      clinical relevance of these alleles in this population with larger sample size.
FAU - John, Shobana
AU  - John S
AD  - Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of 
      Songkla University, Songkhla, Hat Yai 90110, Thailand.
FAU - Balakrishnan, Karuppiah
AU  - Balakrishnan K
AD  - Department of Immunology, School of Biological Sciences, Madurai Kamaraj 
      University, Madurai 625021, Tamil Nadu, India.
FAU - Sukasem, Chonlaphat
AU  - Sukasem C
AUID- ORCID: 0000-0003-0033-5321
AD  - Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, 
      Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, 
      Thailand.
AD  - Laboratory for Pharmacogenomics, SomdechPhraDebaratana Medical Center (SDMC), 
      Ramathibodi Hospital, Bangkok 10400, Thailand.
FAU - Anand, Tharmarajan Chinnathambi Vijay
AU  - Anand TCV
AD  - Department of Neurology, Meenakshi Mission Hospital and Research Center, Madurai 
      625107, Tamil Nadu, India.
FAU - Canyuk, Bhutorn
AU  - Canyuk B
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, 
      Prince of Songkla University, Songkhla, Hat Yai 90110, Thailand.
FAU - Pattharachayakul, Sutthiporn
AU  - Pattharachayakul S
AD  - Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of 
      Songkla University, Songkhla, Hat Yai 90110, Thailand.
LA  - eng
PT  - Journal Article
DEP - 20210728
PL  - Switzerland
TA  - J Pers Med
JT  - Journal of personalized medicine
JID - 101602269
PMC - PMC8400937
OTO - NOTNLM
OT  - CYP2C9*3
OT  - HLA B
OT  - India
OT  - South India
OT  - anti-epileptic drugs (AEDS)
OT  - cutaneous adverse drug reactions (CADRs)
OT  - genetic risk factors
OT  - phenytoin (PHT)
COIS- All authors declare no conflicts of interest.
EDAT- 2021/08/28 06:00
MHDA- 2021/08/28 06:01
PMCR- 2021/07/28
CRDT- 2021/08/27 01:12
PHST- 2021/07/01 00:00 [received]
PHST- 2021/07/25 00:00 [revised]
PHST- 2021/07/26 00:00 [accepted]
PHST- 2021/08/27 01:12 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/08/28 06:01 [medline]
PHST- 2021/07/28 00:00 [pmc-release]
AID - jpm11080737 [pii]
AID - jpm-11-00737 [pii]
AID - 10.3390/jpm11080737 [doi]
PST - epublish
SO  - J Pers Med. 2021 Jul 28;11(8):737. doi: 10.3390/jpm11080737.