GENOMES AND GENETICS

Volume 13, No. 02-03, Month MAY, Year 2020, Pages 59 - 68

Can the snp on tcf19 and pou5f1 predict risk in allopurinol-induced severe cutaneous adverse drug reactions in thai patients

Thawinee Jantararoungtong, Gaidganok Sornsamdang, Santirat Prommas, Napatrupron Koomdee, Apichaya Puangpetch, Patompong Satapornpong, Therdpong Tempark, Pawinee Rerknimitr, Jettanong Klaewsongkram, Papapit Tuchinda, Leena Chularojanamontri, Napatra Tovanabutra, Kumutnart Chanprapaph, Wareeporn Disphanurat, Panlop Chakkavittumrong, Chutika Srisuttiyakorn, Ticha Rerkpattanapipat, Chonlaphat Sukasem

Abstract Download PDF

The aim of this study was to investigate the association of Human leukocyte antigen B (HLA-B), Transcription Factor 19 (TCF19) and POU Class 5 Homeobox 1 (POU5F1) genes with allopurinol-induced cutaneous adverse drug reactions (cADRs), including Stevens-Johnson syndrome/ toxic epidermal necrosis (SJS/TEN; n=21), drug rash with eosinophilia and systemic symptoms (DRESS; n=16) and maculopapular exanthema (MPE; n=7) in Thai patients. This case-control association study compares 44 cases with allopurinol-induced cADR with allopurinol-tolerant control patients (n=100) and a population control group (n=1,095). The control group comprised patients who had received allopurinol for more than 6 months without any adverse cutaneous event. HLA alleles were genotyped using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP).Variants in TCF19 (rs9263794 and rs1044870) and POU5F1 (rs9263796) were genotyped. The risk of allopurinol-induced cADR was significantly higher in the patients with HLA-B*58:01 allele with an odds ratio 240 (95%CI: 57.19–1007.08, p<0.001). In addition, the single nucleotide polymorphisms were also significantly associated with the allopurinol-induced cADR (rs9263794; OR 57.20, p< 0.001, rs1044870; OR 77.31, p< 0.001 and rs9263796; OR 84.14, p<0.001) Furthermore, we found that gender, at the initiation of treatment was associated with allopurinol-induced cADR (OR 59.00, 95%CI: 19.57–98.42, p<0.01). These results suggest that screening tests for HLA-B*58:01 alleles in patients who will be treated with low dosage of allopurinol will be clinically helpful in preventing the risk of developing DRESS, SJS/TEN and MPE in Thai population.

Keywords

HLA-B*58:01; allopurinol; Thai; SCAR; cADR; drug hypersensitivity

---