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

Virginia Leiro-Fernández,Diana Valverde,Alberto Fernández-Villar,Rafael Vázquez-Gallardo,Víctor Del Campo-Pérez,Lucía Constenla-Caramés

doi:10.3389/fmed.2016.00034

Abstract

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. 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. 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.

Highlights

Tuberculosis (TB) continues to be a global health problem despite the availability of effective therapies
The purpose of this study is to evaluate the risk of ATD-induced hepatotoxicity (ATDH) related to Human leukocyte antigen (HLA) class II DQB1*0201 and DQA1*0102 in a cohort of TB patients of Caucasian origin from Spain
We can conclude that even the absence of HLADQA1*0102 could be a risk factor associated with ATDH risk, we cannot demonstrate this association in a cohort of TB patients from Caucasian origin Spanish

Summary

Introduction

Tuberculosis (TB) continues to be a global health problem despite the availability of effective therapies. Hepatotoxicity is one of the most important side effects of first-line antituberculosis drugs (ATD) that could lead to increase in morbidity disease because of treatment interruptions and negative impact in treatment compliance including increasing costs [1, 2]. Genetic susceptibility to ATDH has been the subject of study during last years focusing in genes encoding phase I and II metabolic enzymes, and the risk has been significantly associated with certain genetic polymorphisms [3, 6,7,8,9,10,11]. Even that the majority of recently published studies on ATDH have been concerned with polymorphisms affecting drug-metabolizing enzymes, there are evidence that some HLA class II alleles are related to the risk of ATDH in the Indian and Chinese population [12, 13]. The purpose of this study is to evaluate the risk of ATDH related to HLA class II DQB1*0201 and DQA1*0102 in a cohort of TB patients of Caucasian origin from Spain

Objectives

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Results

Discussion

Conclusion