SLCO1B1 rs4149056 genetic polymorphism predicting methotrexate toxicity in Chinese patients with non-Hodgkin lymphoma

Pharmacogenomics. 2017 Nov;18(17):1557-1562. doi: 10.2217/pgs-2017-0110. Epub 2017 Nov 2.

Abstract

Aim: To investigate the impact of polymorphisms in the FPGS, GGH and SLCO1B1 genes on high dose methotrexate (HD-MTX) related toxicity in Chinese patients with non-Hodgkin lymphoma (NHL).

Materials & methods: We analyzed FPGS (rs10106), GGH (rs719235, rs10464903, rs12681874), SLCO1B1 (rs4149056) genetic polymorphisms in 105 Chinese patients with NHL treated with HD-MTX.

Results: There was a statistically significant impact of the SLCO1B1 rs4149056 polymorphism on hepatotoxicity. Patients with TC and CC genotype had more hepatotoxicity than TT genotype (60 vs 32.94%, p = 0.025). After adjusting for disease stage, dosage, infusion time and therapy method, SLCO1B1 rs4149056 genotype remained significantly associated with hepatotoxicity (p = 0.028).

Conclusion: SLCO1B1 rs4149056 genetic variants can affect the HD-MTX-related toxicity in Chinese patients with NHL.

Keywords: FPGS; GGH; SLCO1B1; gene polymorphism; methotrexate; non-Hodgkin lymphoma; toxicity.

MeSH terms

  • Aged
  • Asian People / genetics*
  • Female
  • Genotype
  • Humans
  • Liver-Specific Organic Anion Transporter 1 / genetics*
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / genetics*
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • Liver-Specific Organic Anion Transporter 1
  • SLCO1B1 protein, human
  • Methotrexate