Influence of pharmacogenomic polymorphisms on allopurinol-induced cutaneous adverse drug reactions in Thai patients
Issued Date
2024-12-01
Resource Type
eISSN
17558794
Scopus ID
2-s2.0-85191056042
Journal Title
BMC Medical Genomics
Volume
17
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
BMC Medical Genomics Vol.17 No.1 (2024)
Suggested Citation
Sornsamdang G., Satapornpong P., Jinda P., Jantararoungtong T., Koomdee N., Tempark T., Klaewsongkram J., Rerkpattanapipat T., Rerknimitr P., Tuchinda P., Chularojanamontri L., Tovanabutra N., Chanprapaph K., Disphanurat W., Chakkavittumrong P., Srisuttiyakorn C., Srinoulprasert Y., John S., Biswas M., Sukasem C. Influence of pharmacogenomic polymorphisms on allopurinol-induced cutaneous adverse drug reactions in Thai patients. BMC Medical Genomics Vol.17 No.1 (2024). doi:10.1186/s12920-024-01874-y Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98150
Title
Influence of pharmacogenomic polymorphisms on allopurinol-induced cutaneous adverse drug reactions in Thai patients
Author(s)
Author's Affiliation
Ramathibodi Hospital
Siriraj Hospital
Rangsit University
University of Liverpool
Bumrungrad International Hospital
University of Rajshahi
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Faculty of Medicine, Thammasat University
Burapha University
Phramongkutklao College of Medicine
Faculty of Medicine, Chulalongkorn University
Chiang Mai University
The Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) Research Group
Siriraj Hospital
Rangsit University
University of Liverpool
Bumrungrad International Hospital
University of Rajshahi
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Faculty of Medicine, Thammasat University
Burapha University
Phramongkutklao College of Medicine
Faculty of Medicine, Chulalongkorn University
Chiang Mai University
The Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) Research Group
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Allopurinol has been causing substantial morbidity and mortality particularly in Asian population by producing cutaneous adverse drug reactions (cADRs). Nonetheless, there are no data describing whether other genetics are a valid marker for prediction of allopurinol-induced cADRs patients in addition to HLA-B*58:01 allele. The goal of this study was to identify suitable single nucleotide polymorphisms (SNPs) for allopurinol induced cADRs among Thai patients. Methods: We conducted a case-control association study after enrolling 57 Thai patients with allopurinol induced cADRs and 101 allopurinol-tolerant controls. The genetic biomarkers and associated SNPs located on chromosome 6p21 were examined by TaqMan® SNP genotyping assays in both the cases and the controls. Results: Out of fifteen SNPs in nine genes, we found four combined SNPs (rs3099844 of HCP5, rs9263726 of PSORS1C1, rs9263733 of POLR2LP, and rs9263745 of CCHCR1) were significantly associated with allopurinol-induced cADRs compared to the tolerant controls (OR 73.2; 95% CI 24.2–266.8; P = 1.9 × 10− 24). The overall sensitivity, specificity, positive predictive value and negative predictive value of these combinations were 84%, 94%, 9%, and 100%, respectively. However, the variant alleles of these SNP combinations were detected in 89.5% (51/57) of the cases. Moreover, the HLA-B*58:01 allele was observed in 86.0% of patients with allopurinol-induced cADRs, but only in 4.0% of tolerant controls (OR: 137.2; 95% CI: 38.3–670.5 and p-value = 1.7 × 10− 27). Conclusions: Thus, this research confirms the association between the specific HLA-B*58:01 allele and all phenotypes of allopurinol-induced cADRs in Thais. Furthermore, there was found the combined four SNPs (rs3099844, rs9263726, rs9263733, and rs9263745) could be used as alternative novel biomarkers for predicting cADRs in patients taking allopurinol.