HLA-B*59:01: a marker for Stevens–Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese

Abstract

Methazolamide is an intraocular pressure-lowering drug that is used in the treatment of glaucoma and other ophthalmologic abnormalities. The use of methazolamide has been shown to cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients of Asian ancestry. Methazolamide-induced SJS/TEN is associated with the presence of HLA-B59 serotype/HLA-B*59:01 in Korean and Japanese populations. To better understand the genetic risk factors for these adverse reactions in the Han Chinese population, we characterized the HLA class I genotypes of eight Chinese patients with methazolamide-induced SJS/TEN from 2008 to 2014. The frequency of HLA-B*59:01 was 87.5% (7/8) in the case patients, which was significantly different from 0% (0/30) in the methazolamide-tolerant patients (odds ratio (OR)=305.0; P=6.3 × 10(-7)) and 0.35% (1/283) in healthy subjects from the human major histocompatibility complex database (OR=1974.0; P=2.0 × 10(-12)). HLA-C*01:02, which is closely linked to HLA-B*59:01, had a weaker but notable association with methazolamide-induced SJS/TEN compared with the tolerant controls (OR=12.1; P=0.016) and general population (OR=15.5; P=2.0 × 10(-3)). The distribution of the HLA-B*59:01-C*01:02 haplotype was also significantly different in cases and controls. This study demonstrated a strong association between HLA-B*59:01 and methazolamide-induced SJS/TEN in the Han Chinese population for the first time. Pretherapy screening for HLA-B*59:01 would be useful to reduce the risk of methazolamide-induced SJS/TEN.

Genetic Diversity of HLA Class I and Class II Alleles in Thai Populations: Contribution to Genotype-Guided Therapeutics

“…In terms of HLA-A*31:01 (IMGT/HLA ID: HLA00097) allele which associates with CBZ-induced CADRs, neither the frequencies within Thailand nor among different populations were significantly different ( Tables 7, 8A). HLA-B*58:01 (IMGT/HLA ID: HLA00386) allele was similarly distributed in Thais (6.38%), African Americans (6.37%), and Asians (7.38%) (Yang et al, 2016) and higher than those reported in Caucasians (Cao et al, 2001), Hispanics (Cao et al, 2001), and North Americans (Cao et al, 2001) ( Tables 7, 8A). However, HLA-B*58:01 allele was not significantly different across different populations.…”

Methazolamide‐induced toxic epidermal necrolysis in a man carrying HLA‐B*59:01: successful treatment with infliximab and glucocorticoid

“…reported that HLA‐B*59:01 was strongly linked with methazolamide‐induced SJS/TEN in both the Japanese and Korean populations. Yang et al . also demonstrated a similar association in eight Han Chinese patients.…”

“…Methazolamide, a sulfonamide derivative, is indicated in the treatment of glaucoma. Several case reports of methazolamide‐induced SJS/TEN have primarily been reported in the context of HLA‐B59 in the Japanese, Korean, and Chinese populations . A correlation between HLA‐B59 and methazolamide‐induced SJS/TEN was initially suggested in a Japanese patient in 1997 .…”

Human leucocyte antigen–adverse drug reaction associations: from a perspective of ethnicity

“…Methazolamide is a carbonic anhydrase inhibitor used to treat glaucoma. It has been reported to be associated with SJS/TEN in Han Chinese patients (Yang et al ., ). The study reported associations with the haplotype HLA‐B*59:01‐HLA‐C*01:02.…”