Validation of a genotyping technique for a surrogate marker of HLA-B∗58:01 for allopurinol-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in the Japanese population

• Published in: Drug metabolism and pharmacokinetics 2023-04, Vol.49, p.100495-100495, Article 100495
• Main Authors: Tsukagoshi, Eri, Nakamura, Ryosuke, Tanaka, Yoichi, Maekawa, Keiko, Hiratsuka, Masahiro, Asada, Hideo, Saito, Yoshiro
• Format: Article
• Language: English
• Subjects: Allopurinol; Biomarkers; East Asian People; Genotype; Genotyping Techniques; HLA-B Antigens - genetics; Human leukocyte antigen; Humans; Screening test; Single-nucleotide polymorphism; Stevens-Johnson Syndrome - genetics; Stevens–Johnson syndrome; Toxic epidermal necrolysis
• ISSN: 1347-4367; 1880-0920
• DOI: 10.1016/j.dmpk.2023.100495

Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare but severe cutaneous adverse drug reactions. Certain human leukocyte antigen (HLA) types have been associated with SJS/TEN onset, e.g., HLA-B∗58:01 with allopurinol-induced SJS/TEN, but HLA typing is time-consuming and expensive; thus, it is not commonly used in clinical situations. In the previous work, we demonstrated that the single-nucleotide polymorphisms (SNP) rs9263726 was in absolute linkage disequilibrium with HLA-B∗58:01 in the Japanese population, and can be used as a surrogate marker for the HLA. Here, we developed a new genotyping method for the surrogate SNP using the single-stranded tag hybridization chromatographic printed-array strip (STH-PAS) technique and performed an analytical validation. The results of genotyping rs9263726 using STH-PAS correlated well with those obtained using the TaqMan SNP Genotyping Assay for 15 HLA-B∗58:01-positive and 13 HLA-B∗58:01-negative patients (analytical sensitivity and specificity were both 100%). Additionally, at least 1.11 ng of genomic DNA was sufficient to digitally and manually detect positive signals on the strip. Robustness studies showed that the annealing temperature (66 °C) was the most important condition related to reliable results. Collectively, we developed an STH-PAS method that can rapidly and easily detect rs9263726 for predicting SJS/TEN onset.