Genetic susceptibilities and prediction modeling of carbamazepine and allopurinol-induced severe cutaneous adverse reactions in Vietnamese

Pharmacogenomics. 2021 Jan;22(1):1-12. doi: 10.2217/pgs-2019-0146. Epub 2020 Dec 24.

Abstract

Aims: To determine genetic susceptibility markers for carbamazepine (CBZ) and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese. Methods: A case-control study was performed involving 122 patients with CBZ or allopurinol-induced SCARs and 120 drug tolerant controls. Results:HLA-B*58:01 was strongly associated with allopurinol-induced SCARs and strongly correlated with SNP rs9263726. HLA-B*15:02 was associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis but not with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms. No association was found between HLA-A*31:01 and CBZ-induced SCARs. HLA-B*58:01 and rs3909184 allele A with renal insufficiency were shown to increase the risk of allopurinol-induced SCARs. Conclusion:HLA-B*58:01 and HLA-B*15:02 confer susceptibility to allopurinol-induced SCARs and CBZ-induced SJS/TEN in Vietnamese. SNP rs9263726 can be used as a surrogate marker in identifying HLA-B*58:01.

Keywords: DRESS; HLA; SJS/TEN; Vietnamese; allopurinol; carbamazepine; severe cutaneous adverse drug reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Allopurinol / adverse effects*
  • Anticonvulsants / adverse effects
  • Asian People / genetics*
  • Carbamazepine / adverse effects*
  • Case-Control Studies
  • Female
  • Forecasting
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics*
  • Gout Suppressants / adverse effects
  • HLA-B Antigens / genetics*
  • Humans
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Stevens-Johnson Syndrome / diagnosis
  • Stevens-Johnson Syndrome / epidemiology
  • Stevens-Johnson Syndrome / genetics*
  • Vietnam / epidemiology
  • Young Adult

Substances

  • Anticonvulsants
  • Gout Suppressants
  • HLA-B Antigens
  • HLA-B*58:01 antigen
  • Carbamazepine
  • Allopurinol