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NAT2, CYP2C9, CYP2C19, and CYP2E1 genetic polymorphisms in anti-TB drug-induced maculopapular eruption

Sang-Heon Kim1, Sang-Hoon Kim, Ho Joo Yoon

  • 1Department of Internal Medicine, Hanyang University College of Medicine, Haengdang-dong 17, Seongdong-gu, Seoul, Korea.

European Journal of Clinical Pharmacology
|October 14, 2010
PubMed
Abstract

Insights

Genetic variations in CYP2C19 and CYP2C9 influence the risk of anti-tuberculosis drug (ATD)-induced maculopapular eruption (MPE). These findings suggest a role for these drug-metabolizing enzymes in ATD adverse reactions.

Area of Science:

  • Pharmacogenomics
  • Tuberculosis Treatment
  • Adverse Drug Reactions

Background:

  • Drug-metabolizing enzymes are implicated in anti-tuberculosis drug (ATD)-induced hepatitis.
  • The role of these enzymes in ATD-induced maculopapular eruption (MPE) is not well understood.

Purpose of the Study:

  • To investigate the association between genetic polymorphisms in drug-metabolizing enzymes and the development of ATD-induced MPE.
  • To compare genetic variations in patients with and without ATD-induced MPE.

Main Methods:

  • A case-control study involving 62 patients with ATD-induced MPE and 159 ATD-tolerant patients with tuberculosis.
  • Genotype distributions of single nucleotide polymorphisms and haplotypes in NAT2, CYP2C9, CYP2C19, and CYP2E1 were analyzed.
  • Multivariate logistic regression was used to assess associations.

Main Results:

  • CYP2C9 polymorphism (-1565 C>T) was significantly associated with a lower risk of ATD-induced MPE (P=0.022, OR=0.23).
  • CYP2C19 polymorphism (W212X) also showed a significant association with reduced MPE risk (P=0.042, OR=0.27).
  • A specific CYP2C19-CYP2C9 haplotype (ht3[T-A-T-C]) was strongly associated with a decreased risk of MPE (P=0.012, OR=0.13).

Conclusions:

  • Genetic polymorphisms in CYP2C19 and CYP2C9 are significantly associated with the risk of developing ATD-induced MPE.
  • Genetic variants in NAT2 and CYP2E1 do not appear to be closely related to ATD-induced MPE development.

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