In:
Pharmacogenetics and Genomics, Ovid Technologies (Wolters Kluwer Health), Vol. 30, No. 7 ( 2020-9), p. 153-160
Abstract:
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
Type of Medium:
Online Resource
ISSN:
1744-6872
DOI:
10.1097/FPC.0000000000000408
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2020
detail.hit.zdb_id:
2048376-4
SSG:
15,3
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