NR3C1, ABCB1, TNF and CYP2C19 polymorphisms association with the response to the treatment of erythema nodosum leprosum

Pharmacogenomics. 2019 May;20(7):503-516. doi: 10.2217/pgs-2018-0192.

Abstract

Aim: To evaluate the effects of gene polymorphisms in the treatment of erythema nodosum leprosum with prednisone/thalidomide. Patients & methods: A total of 152 patients from different regions of Brazil were included. Generalized estimating equation was used to evaluate the influence of polymorphisms and haplotypes on the drug dose variation throughout the treatment. Results: An association between the genotype tuberculoid of polymorphism ABCB1 3435C>T (rs1045642; p = 0.02) and prednisone dose was found in the recessive model. An association between the haplotypes 1031T/-863C/-857C/-308A/-238G (p = 0.006) and 1031T/-863C/-857T/-308A/-238G (p = 0.040) of the TNF gene and the CYP2C19*2 polymorphism were also identified, in relation to thalidomide dosage variation over the course of treatment. Conclusion: This work presents the first pharmacogenetic report of association between gene polymorphisms and erythema nodosum leprosum treatment with prednisone/thalidomide.

Keywords: erythema nodosum leprosum; pharmacogenomics; treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adult
  • Brazil / epidemiology
  • Cytochrome P-450 CYP2C19 / genetics*
  • Dose-Response Relationship, Drug
  • Erythema Nodosum / drug therapy*
  • Erythema Nodosum / genetics
  • Erythema Nodosum / pathology
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Male
  • Polymorphism, Genetic
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Receptors, Glucocorticoid / genetics
  • Thalidomide / administration & dosage
  • Thalidomide / adverse effects
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • NR3C1 protein, human
  • Receptors, Glucocorticoid
  • Tumor Necrosis Factor-alpha
  • Thalidomide
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Prednisone