Influence of glutathione S‐transferase M1 and T1 homozygous null mutations on the risk of antituberculosis drug‐induced hepatotoxicity in a Caucasian population

Abstract

The GSTT1 homozygous null polymorphism may be a risk factor of antituberculosis drug-induced hepatotoxicity in Caucasians.

Glutathione S-transferase M1 and T1 null genotypes increase susceptibility to drug-induced liver injury #

“…Our group performed the first study with 95 Caucasian patients originally from Spain to investigate the influence of these null polymorphisms on the risk of antituberculosis drug-induced hepatotoxicity and showed an enhanced risk of DILI in GSTT1-null carriers (odds ratio ϭ 2.6; P ϭ 0.03). 8 The frequency of double GSTM1 and GSTT1 genotype carriers was higher in cases than in controls; however, these differences did not reach significance because the power of the associations related to the small size of the patient subgroup. The study by Lucena et al corroborated this observation.…”

Biotransformation Enzymes for Xenobiotics and Personalization of Treatment Regimens for Tuberculosis Patients

“…вы званной ксенобиотикам и, связы ваю т с на личием нулевы х аллелей G ST T 1*0 или G ST M 1*0. В некоторы х и сследован и ях повы ш енны й риск геп атотокси чн ости при прием е П ТП н аблю дал ся у пациентов, гом озиготны х по G S T M 1 * 0 [18,21]. О д н ак о в и сследован и и [21] повы ш енны й риск развития гепатотоксичности.…”

Polymorphisms in CYP2E1, GSTM1 and GSTT1 and anti-tuberculosis drug-induced hepatotoxicity

“…Whole GSTM1 and GSTT1 genes show high percentage of deletion in the human population (Bolt and Thier, 2006) and this is expected to contribute to interindividual differences in response to xenobiotics (Hayes et al 2005). GSTM1 and GSTT1 deletions are the best choices for druginduced liver injury in association studies (Roy et al 2001, Hussain et al 2003, Leiro et al 2008, Huang, 2010.…”

“…For the second analysis, primers designed by other authors were used (Leiro et al 2008). GSTs were considered present when the fragment was amplified together 858 TAIS C. BRITO et al with the 560 bp NAT2 DNA fragment, used as an internal control.…”

“…Frequency and severity of anti-TB druginduced hepatotoxicity is variable and unpredictable. Secondary pathways and the metabolizing profile take part in the unbalance between hepatotoxin production and liver detoxification (Roy et al 2001, Leiro et al 2008. Our previous study of NAT2 polymorphism demonstrated that a slow acetylation profile is associated to ATD-induced hepatitis (Possuelo et al 2008).…”