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The association between HLA-B variants and amoxicillin-induced severe cutaneous adverse reactions in Chinese han

Ting Wang1, Jin Yang2,3,4, Fanping Yang2,3,4

  • 1Children's Hospital of Fudan University, Institutes of Biomedical Sciences of Fudan, Shanghai, China.

Frontiers in Pharmacology
|June 12, 2024
PubMed
Abstract

Insights

Genetic factors, specifically HLA-B*15:01, are strongly associated with amoxicillin-induced severe cutaneous adverse reactions (AMX-SCAR). This discovery may help identify individuals at risk for AMX-SCAR and guide safer antibiotic prescribing.

Area of Science:

  • Pharmacogenomics
  • Immunogenetics
  • Dermatology

Background:

  • Amoxicillin (AMX) is a widely used antibiotic with a generally good safety profile.
  • Severe cutaneous adverse reactions (SCAR) to AMX, though rare, carry significant morbidity and mortality.
  • The genetic underpinnings of AMX-SCAR are not well understood, hindering personalized risk assessment.

Purpose of the Study:

  • To identify genetic risk factors associated with amoxicillin-induced severe cutaneous adverse reactions (AMX-SCAR).
  • To investigate the role of Human Leukocyte Antigen (HLA) genes in AMX-SCAR susceptibility.
  • To explore the molecular mechanisms of AMX-SCAR through computational analysis.

Main Methods:

  • Case-control study involving four AMX-SCAR patients, 1,000 population controls, and 100 AMX-tolerant individuals.
  • Exome-wide and HLA-specific association studies were performed.
  • Molecular docking simulations were used to analyze drug-protein interactions.

Main Results:

  • A significant association was found between HLA-B*15:01 and AMX-SCAR (OR=22.9, p=7.34 × 10^-3).
  • The S140 epitope within the HLA-B protein showed a strong association with AMX-SCAR (OR=53.5, p=5.18 × 10^-4).
  • Molecular docking confirmed direct interaction between AMX and the HLA-B S140 epitope.

Conclusions:

  • Genetic susceptibility, particularly involving HLA-B variants, plays a role in AMX-SCAR development in the Han Chinese population.
  • HLA-B*15:01 may serve as a potential genetic marker for predicting AMX-SCAR risk.
  • Further validation in larger, diverse populations is warranted to confirm these findings and their clinical utility.
Keywords:
HLA-Bamoxicillinsevere cutaneous adverse reactionsvariantswhole-exome sequencing

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