Association between genetic polymorphisms of SLCO1B1 and susceptibility to methimazole-induced liver injury

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Shasha Jin1, Xuesong Li2, Yujuan Fan2

  • 1Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, China.

Basic & Clinical Pharmacology & Toxicology
|June 27, 2019
PubMed

Insights

Genetic variations in SLCO1B1 may increase susceptibility to methimazole-induced liver injury in Grave's disease patients. Further research into these genetic factors could help predict and prevent adverse drug reactions.

Area of Science:

  • Pharmacogenomics
  • Hepatology
  • Endocrinology

Background:

  • Methimazole (MMI) is a primary treatment for Grave's disease (GD).
  • Drug-induced liver injury (DILI) is a significant adverse effect of MMI therapy.
  • Genetic factors influencing MMI-DILI susceptibility are not fully understood.

Purpose of the Study:

  • To investigate the association between genetic polymorphisms in drug-metabolizing enzymes and transporters and MMI-DILI.
  • To identify genetic markers that predict MMI-DILI risk in GD patients.

Main Methods:

  • Genotyping of 33 single nucleotide polymorphisms (SNPs) in 20 candidate genes in 44 GD patients with MMI-DILI and 118 controls.
  • Association analysis of SNPs with MMI-DILI.
  • Haplotype analysis of SLCO1B1 gene.

Main Results:

  • Several SNPs (rs12422149 in SLCO2B1, rs2032582_AT in ABCB1, rs2306283 in SLCO1B1, rs4148323 in UGT1A1) showed preliminary association with MMI-DILI, though not significant after Bonferroni correction.
  • Haplotype SLCO1B1*1a (388A521T) was more frequent in MMI-DILI cases (OR=2.21).
  • Haplotype SLCO1B1*1b (388G521T) was more frequent in the control group (OR=0.52).

Conclusions:

  • Genetic polymorphisms in the SLCO1B1 gene are associated with susceptibility to MMI-DILI.
  • SLCO1B1 genetic variations may serve as predisposing factors for MMI-induced hepatotoxicity.
Keywords:
SLCO1B1Grave's diseasedrug-induced liver injurymethimazolepolymorphisms

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