The Association of HLA-B*35 and GSTT1 Genotypes and Hepatotoxicity in Thai People Living with HIV

Author:

Chanhom NoppadolORCID,Jittikoon Jiraphun,Wattanapokayakit Sukanya,Mahasirimongkol Surakameth,Charoenyingwattana Angkana,Udomsinprasert Wanvisa,Chaikledkaew Usa,Suvichapanich Supharat,Mushiroda Taisei,Kiertiburanakul Sasisopin,Rojanawiwat Archawin,Wangsomboonsiri Wittaya,Manosuthi Weerawat,Kantipong Pacharee,Apisarnthanarak Anucha,Sangsirinakakul Wilawan,Wongprasit Pawinee,Chaiwarith RomaneeORCID,Tantisiriwat Woraphot,Sungkanuparph SomnuekORCID,Chantratita Wasun

Abstract

Glutathione s-transferase (GST) is a family of drug-metabolizing enzymes responsible for metabolizing and detoxifying drugs and xenobiotic substances. Therefore, deletion polymorphisms of GSTs can be implicated in developing several pathological conditions, including antiretroviral drug-induced liver injury (ARVDILI). Notably, GST polymorphisms have been shown to be associated with ARVDILI risk. However, data on GST polymorphisms in the Thai population are limited. Therefore, this study investigated possible associations between GST genetic polymorphisms and ARVDILI development. A total of 362 people living with HIV (PLHIV) and 85 healthy controls from multiple centers were enrolled. GSTM1 and GSTT1 genetic polymorphisms were determined using polymerase chain reactions. In addition, HLA genotypes were determined using a sequence-based HLA typing method. After comparing GST genotypic frequencies, there was no significant difference between PLHIV and healthy volunteers. However, while observing the PLHIV group, GSTT1 wild type was significantly associated with a 2.04-fold increased risk of ARVDILI (95%CI: 1.01, 4.14; p = 0.045). Interestingly, a combination of GSTT1 wild type and HLA-B*35:05 was associated with a 2.28-fold higher risk of ARVDILI (95%CI: 1.15, 4.50; p = 0.02). Collectively, GSTT1 wild type and a combination of GSTT1 wild type plus HLA-B*35:05 were associated with susceptibility to ARVDILI in the Thai population.

Funder

Thailand Research Fund

e-ASIA Joint Research Program

Health Systems Research Institute

Publisher

MDPI AG

Subject

Medicine (miscellaneous)

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