PMID- 32433341
OWN - NLM
STAT- MEDLINE
DCOM- 20210308
LR  - 20211204
IS  - 1744-6880 (Electronic)
IS  - 1744-6872 (Linking)
VI  - 30
IP  - 7
DP  - 2020 Sep
TI  - HLA-B*58: 01 association in allopurinol-induced severe cutaneous adverse 
      reactions: the implication of ethnicity and clinical phenotypes in multiethnic 
      Malaysia.
PG  - 153-160
LID - 10.1097/FPC.0000000000000408 [doi]
AB  - OBJECTIVE: The association between human leukocyte antigen (HLA)-B*58:01 and risk 
      of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed 
      across different populations. We explore the association between HLA-B*58:01 and 
      AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different 
      AIS clinical phenotypes and ethnicity was determined. METHODS: We performed a 
      case-control association study by genotyping the HLA-B alleles of 55 patients 
      with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 
      22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute 
      generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls 
      (ATC). RESULTS: HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC 
      study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, 
      P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN 
      patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive 
      (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% 
      CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes 
      revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS 
      patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese 
      patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was 
      positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations 
      of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P 
      < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although 
      the number of Indian-AIS patients was relatively small (n = 2), both were 
      HLA-B*58:01 positive. CONCLUSION: Our data suggest strong associations between 
      HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. 
      The strong association was also observed in three different clinical phenotypes 
      of AIS, mainly the AIS-SJS/TEN.
FAU - Low, Dyoi E
AU  - Low DE
AD  - Department of Dermatology, Hospital Kuala Lumpur, Ministry of Health Malaysia.
AD  - Department of Dermatology, Hospital Serdang, Ministry of Health Malaysia.
FAU - Nurul-Aain, Ahmad Fauzi
AU  - Nurul-Aain AF
AD  - Immunogenetic Unit, Allergy and Immunology Research Center, Institute for Medical 
      Research, Ministry of Health Malaysia, Kuala Lumpur.
FAU - Tan, Wooi Chiang
AU  - Tan WC
AD  - Department of Dermatology, Hospital Serdang, Ministry of Health Malaysia.
FAU - Tang, Jyh Jong
AU  - Tang JJ
AD  - Department of Dermatology, Hospital Raja Permaisuri Bainun, Ministry of Health 
      Malaysia, Perak.
FAU - Bakhtiar, Mohammed Faizal
AU  - Bakhtiar MF
AD  - Allergy Unit, Allergy and Immunology Research Center, Institute for Medical 
      Research, Ministry of Health Malaysia, Kuala Lumpur.
FAU - Murad, Shahnaz
AU  - Murad S
AD  - Office of Deputy Director General of Health, Ministry of Health Malaysia, 
      Putrajaya.
FAU - Chang, Choong Chor
AU  - Chang CC
AD  - Gleneagles Kuala Lumpur, Jalan Ampang, Kuala Lumpur, Malaysia.
FAU - Too, Chun Lai
AU  - Too CL
AD  - Immunogenetic Unit, Allergy and Immunology Research Center, Institute for Medical 
      Research, Ministry of Health Malaysia, Kuala Lumpur.
FAU - Tang, Min Moon
AU  - Tang MM
AD  - Department of Dermatology, Hospital Kuala Lumpur, Ministry of Health Malaysia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pharmacogenet Genomics
JT  - Pharmacogenetics and genomics
JID - 101231005
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*58:01 antigen)
RN  - 63CZ7GJN5I (Allopurinol)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Allopurinol/*adverse effects
MH  - Case-Control Studies
MH  - Drug Eruptions/*genetics
MH  - Ethnicity/*genetics
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - HLA-B Antigens/*genetics
MH  - Humans
MH  - Malaysia/ethnology
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Young Adult
EDAT- 2020/05/21 06:00
MHDA- 2021/03/09 06:00
CRDT- 2020/05/21 06:00
PHST- 2020/05/21 06:00 [pubmed]
PHST- 2021/03/09 06:00 [medline]
PHST- 2020/05/21 06:00 [entrez]
AID - 01213011-202009000-00002 [pii]
AID - 10.1097/FPC.0000000000000408 [doi]
PST - ppublish
SO  - Pharmacogenet Genomics. 2020 Sep;30(7):153-160. doi: 
      10.1097/FPC.0000000000000408.