Dataset Information

HLA-DQ B10201 and A10102 Alleles Are Not Responsible for Antituberculosis Drug-Induced Hepatotoxicity Risk in Spanish Population.

ABSTRACT:

Aims

To evaluate the role of human leukocyte antigen (HLA) class II DQB1*0201 and DQA1*0102 in the risk of antituberculosis drug (ATD)-induced hepatotoxicity (ATDH) in a cohort of tuberculosis patients of Caucasian origin from Spain.

Methods

Matched case-control study including active tuberculosis (TB) patients from Spain (Caucasian) treated with first-line ATD (Isoniazid, Rifampin, and Pyrazinamide). Presence or absence of HLA class II DQB1*0201 and DQA1*0102 alleles were compared between cases and controls.

Results

We included 110 TB patients, 55 ATDH cases, and 55 sex-matched controls. The analysis of the presence of HLA-DQB1*0201 and HLA-DQA*0102 did not show significative differences between both groups [presence of HLA-DQB1*0201 53.6% of the cases vs. 45.4% of the controls, OR: 1.63 95% CI (0.62-4.52) p = 0.38; presence of HLA-DQA*0102 7.5% of cases vs. 20% of controls, OR: 0.36 95% CI (0.08-1.23) p = 0.12]. After multivariate logistic regression analysis including in the model, other potential risk factors of hepatotoxicity HLA class II DQB1*0201 and DQA1*0102 alleles were not found significantly associated with the risk of development ATDH. We could not demonstrate an association between HLA-DQA1*0102 and HLA-DQB1*0201 with the risk of ATDH in this Caucasian population of Spanish origin.

SUBMITTER: Leiro-Fernandez V

PROVIDER: S-EPMC4992991 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

HLA-DQ B10201 and A10102 Alleles Are Not Responsible for Antituberculosis Drug-Induced Hepatotoxicity Risk in Spanish Population.

Leiro-Fernández Virginia V Valverde Diana D Vázquez-Gallardo Rafael R Constenla-Caramés Lucía L Del Campo-Pérez Víctor V Fernández-Villar Alberto A

Frontiers in medicine 20160822

<h4>Aims</h4>To evaluate the role of human leukocyte antigen (HLA) class II DQB1*0201 and DQA1*0102 in the risk of antituberculosis drug (ATD)-induced hepatotoxicity (ATDH) in a cohort of tuberculosis patients of Caucasian origin from Spain.<h4>Methods</h4>Matched case-control study including active tuberculosis (TB) patients from Spain (Caucasian) treated with first-line ATD (Isoniazid, Rifampin, and Pyrazinamide). Presence or absence of HLA class II DQB1*0201 and DQA1*0102 alleles were compare ...[more]

PMID: 27597944

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Project description:BackgroundThe accumulation of the hepatotoxic substance protoporphyrin IX (PPIX) induced by aminolevulinate synthase 1 (ALAS1) activation is one of the important mechanisms of antituberculosis drug-induced hepatotoxicity (ATDH). Forkhead box protein O1 (FOXO1) may activate ALAS1 transcription. However, little is known about their roles in ATDH; we performed a study to determine the association between polymorphisms in the two genes and ATDH susceptibility. Then, we verified this possible association by cellular functional experiments.Materials and methodsTag single-nucleotide polymorphisms (TagSNPs) in the two genes were genotyped in 746 tuberculosis patients. The frequencies of the alleles, genotypes, genetic models, and haplotype distribution of the variants were compared between the case and control groups. L-02 cells and HepG2 cells were incubated with the indicated concentration of isoniazid (INH) and rifampicin (RIF) for the desired times, and then the expression levels of ALAS1 and FOXO1 mRNAs and proteins were detected. HepG2 cells were transiently transfected with FOXO1 siRNA to observe the effect of changes in the FOXO1 expression on the cell survival rate and ALAS1 expression.ResultsThe C allele at rs2755237 and the T allele at rs4435111 in the FOXO1 gene were associated with a decreased risk of ATDH. The expression of ALAS1 in both L-02 cells and HepG2 cells was increased by the coadministration of INH/RIF (600/200 μM) for 24 h. Although FOXO1 expression was reduced slightly by the same treatment, its content in the nucleus was significantly increased. However, the cell survival rate and ALAS1 expression level were not significantly altered by the downregulation of FOXO1 in HepG2 cells.ConclusionsVariants of the rs4435111 and rs2755237 loci in the FOXO1 gene were associated with susceptibility to ATDH. Coadministration of INH/RIF promoted the transfer of FOXO1 from the cytoplasm to the nucleus, but the functional significance of its nuclear translocation requires further verification.

Dataset Information

HLA-DQ B10201 and A10102 Alleles Are Not Responsible for Antituberculosis Drug-Induced Hepatotoxicity Risk in Spanish Population.

Aims

Methods

Results

Publications

HLA-DQ B10201 and A10102 Alleles Are Not Responsible for Antituberculosis Drug-Induced Hepatotoxicity Risk in Spanish Population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

HLA-DQ B1*0201 and A1*0102 Alleles Are Not Responsible for Antituberculosis Drug-Induced Hepatotoxicity Risk in Spanish Population.

Aims

Methods

Results

Publications

HLA-DQ B1*0201 and A1*0102 Alleles Are Not Responsible for Antituberculosis Drug-Induced Hepatotoxicity Risk in Spanish Population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

HLA-DQ B10201 and A10102 Alleles Are Not Responsible for Antituberculosis Drug-Induced Hepatotoxicity Risk in Spanish Population.

HLA-DQ B10201 and A10102 Alleles Are Not Responsible for Antituberculosis Drug-Induced Hepatotoxicity Risk in Spanish Population.