RGD Reference Report - NAT2, CYP2C9, CYP2C19, and CYP2E1 genetic polymorphisms in anti-TB drug-induced maculopapular eruption. - Rat Genome Database

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

Authors: Kim, Sang-Heon  Kim, Sang-Hoon  Yoon, Ho Joo  Shin, Dong Ho  Park, Sung Soo  Kim, Youn-Seup  Park, Jae-Seuk  Jee, Young Koo 
Citation: Kim SH, etal., Eur J Clin Pharmacol. 2011 Feb;67(2):121-7. doi: 10.1007/s00228-010-0912-4. Epub 2010 Oct 13.
RGD ID: 124713543
Pubmed: PMID:20941486   (View Abstract at PubMed)
DOI: DOI:10.1007/s00228-010-0912-4   (Journal Full-text)


PURPOSE: It has been suggested that drug-metabolizing enzymes might play important roles in the development of anti-tuberculosis drug (ATD)-induced maculopapular eruption (MPE), as in ATD-induced hepatitis. We investigated the associations between the genetic polymorphisms of drug-metabolizing enzymes and ATD-induced MPE.
METHODS: We enrolled 62 patients with ATD-induced MPE (mean age 47.2 ± 19.0, male 59.7%) and 159 patients without any adverse reactions to ATD (mean age 42.8 ± 17.6, male 65.4%), among patients with pulmonary tuberculosis (TB) and/or TB pleuritis and treated with first-line anti-TB medications, including isoniazid, rifampin, ethambutol, and pyrazinamide. We compared the genotype distributions of single nucleotide polymorphisms and haplotypes in four drug-metabolizing enzymes (N-acetyltransferase 2 (NAT2), cytochrome P450 (CYP) 2 C9, CYP2C19, and CYP2E1) among patients with ATD-induced MPE and patients tolerant to ATD using a multivariate logistic regression analysis. These analyses were made without identification of the responsible ATD.
RESULTS: -1565 C > T of CYP2C9 showed a significant association with ATD-induced MPE (P = 0.022, OR = 0.23, 95% CI 0.07-0.78), with a lower frequency of genotypes carrying minor alleles (CT or TT) in the case group than in the controls. Additionally, W212X of CYP2C19 was significantly associated with the risk of ATD-induced MPE (P = 0.042, OR = 0.27, 95% CI 0.09-0.82). In an analysis of the CYP2C19-CYP2C9 haplotypes (-1418 C > T_W212X_-1565 C > T_-1188 C > T), ht3[T-A-T-C] showed a significant association with the development of ATD-induced MPE (P = 0.012, OR = 0.13, 95% CI 0.03-0.57). No significant associations between the other genetic polymorphisms and ATD-induced MPE were observed.
CONCLUSIONS: CYP2C19 and CYP2C9 genetic polymorphisms are significantly associated with the risk of developing ATD-induced MPE, and the genetic variants in NAT2 and CYP2E1 are not closely related to the development of this adverse reaction.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Drug Eruptions treatmentIAGP 124713543associated with tuberculosis more ...RGD 
Drug Eruptions treatmentISOCYP2C19 (Homo sapiens)124713543; 124713543associated with tuberculosis more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp2c6  (cytochrome P450, family 2, subfamily C, polypeptide 6)

Genes (Mus musculus)
Cyp2c38  (cytochrome P450, family 2, subfamily c, polypeptide 38)

Genes (Homo sapiens)
CYP2C19  (cytochrome P450 family 2 subfamily C member 19)


Additional Information