3059 Associations of GCLM, gclc and GSTP1 gene polymorphisms and antituberculosis drugs-induced hepatitis

Tuesday, 9 December 2014
Exhibition Hall-Poster Area (Sul America)

Sang-Heon Kim, MD , Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea

Yong Eun Kwon, MD , Department of Internal Medicine, Chosun University College of Medicine, Gwangju, South Korea

Sang-Hoon Kim, MD , Department of Internal Medicine, Eulji University School of Medicine, Seoul, South Korea

Jang Won Sohn, MD , Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea

Ho Joo Yoon , Department of Internal Medicine, Division of Pulmonary Medicine, Hanyang University Hospital, South Korea

Dong Ho Shin, MD , Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea

Sung Soo Park, MD , Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea

Jae Hyung Lee, MD , Department of Internal Medicine, Eulji University School of Medicine, Seoul, South Korea

Byoung-Hoon Lee, MD , Department of Internal Medicine, Eulji University School of Medicine, Seoul, South Korea

Youn-Seup Kim, MD , Department of Internal Medicine, Dankook University College of Medicine, Cheonan, South Korea

Jae-Seuk Park, MD , Department of Internal Medicine, Dankook University College of Medicine, Cheonan, South Korea

Young-Koo Jee, MD , Department of Internal Medicine, Dankook University College of Medicine, Cheonan, South Korea

Background: Antituberculosis drugs (ATD) is the most common cause of drug-induce liver injury in many countries. While the mechanism of ATD-induced hepatitis is poorly understood, oxidative stress is suggested to be involved in the development of liver injury to drug metabolites. In this regards, we explored the possible associations between glutathione related enzymes (GCLM, GCLC and GSTP1) gene polymorphisms and ATD-induced hepatitis.

Methods: Through regular monitoring of liver function test during the treatment of tuberculosis, 84 patients with ATD-induced hepatitis and 237 ATD-tolerant controls were enrolled. Genotype were assessed in 3 single nucleotide polymorphisms in GCLM (rs41303970, -590T>C), GCLC (rs17883901, -594T>C) and GSTP1 (rs1695, I105V) and compared between case and control groups.

Results: No significant difference was found in genotype frequencies of rs41303970, rs17883901 and rs1695 between patients with ATD-induced hepatitis and ATD-tolerant controls in three statistical models (dominant, recessive and codominant model). In addition, the minor allele frequency were not different between case and control group in three polymorphism sites.

Conclusions: There was no significant association between GCLM, GCLC and GSTP1 gene polymorphisms and ATD-induced hepatitis. These findings suggest that genetic variants of GCLM, GCLC and GSTP1 do not increase the risk of ATD-induced hepatitis.