Sodam Jung; Sang-Hoon Kim; Jang Won Sohn; Ho Joo Yoon; Dong Ho Shin; Young-Koo Jee; Sang-Heon Kim

doi:10.4168/aard.2017.5.1.41

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Jung, Kim, Sohn, Yoon, Shin, Jee, and Kim: Genetic polymorphisms of interleukin-10 and transforming growth factor-β1 and antituberculosis drugs-induced liver injury

Original Article

Allergy, Asthma & Respiratory Disease 2017; 5(1): 41-46.

Published online: 31 January 2017

DOI: https://doi.org/10.4168/aard.2017.5.1.41

Genetic polymorphisms of interleukin-10 and transforming growth factor-β1 and antituberculosis drugs-induced liver injury

Sodam Jung¹, Sang-Hoon Kim², Jang Won Sohn¹, Ho Joo Yoon¹, Dong Ho Shin¹, Young-Koo Jee³, Sang-Heon Kim¹

¹Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.

²Department of Internal Medicine, Eulji University School of Medicine, Seoul, Korea.

³Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.

Correspondence to: Sang-Heon Kim. Department of Internal Medicine, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea. Tel: +82-2-2290-8336, Fax: +82-2-2298-9183, sangheonkim@hanyang.ac.kr

Received 9 October 2016 Revised 27 October 2016 Accepted 22 November 2016

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/).

Abstract

Purpose

Drug-induced liver injury is one of the serious adverse reactions resulting in severe morbidity and discontinuation of medications. Previously, IL-10 gene polymorphism has been reported to be associated with diclofenac-induced hepatitis. In this study, we aimed to investigate the associations between genetic polymorphisms of immune-regulating cytokines (IL-10 and TGF-β1) with antituberculosis drugs (ATD)-induced liver injury.

Methods

We enrolled 80 patients with ATD-induced liver injury and 238 ATD-tolerant controls. Two single nucleotide polymorphisms (SNP) of IL-10 (-1082A>G, rs1800896; -819T>C, rs1800871) and one promoter SNP of TGF-β1 gene (-509C>T, rs1800469) were genotyped in both groups. Genotype frequencies of these SNPs were compared between case and control groups.

Results

In 2 promoter SNPs of IL-10 gene, there was no significant difference of genotype frequencies between patients with ATD-induced liver injury and controls. In addition, the genotype frequency of TGF-β1 -509C>T SNP in ATD-induced liver injury patients were not different from those of controls.

Conclusion

In conclusion, there was no significant association between IL-10 and TGF-β1 gene polymorphisms and ATD-induced liver injury. These findings suggest that IL-10 and TGF-β1 do not play important role in the development of ATD-induced liver injury.

Keywords: Antitubercular agents, Drug-induced liver injury, Interleukin-10, Transforming growth factor beta1, Genetic polymorphism

Figures and Tables

Table 1

Single nucleotide polymorphisms tested in this study

Gene	SNP	rs number	Hardy-Weinberg Equilibrium (P-value)
Gene	SNP	rs number	ATD-induced liver injury (n = 80)	ATD-tolerant controls (n = 238)
IL10	−1082A > G	rs1800896	0.895	0.649
IL10	−819T > C	rs1800871	0.815	0.164
TGFB1	−509C > T	rs1800469	1.000	0.759

ATD, antituberculosis drugs; SNP, single nucleotide polymorphism.

Table 2

Clinical characteristics of the study subjects

Characteristic	ATD-induced liver injury (n = 80)	ATD-tolerant controls (n = 238)	P-value
Female sex	37 (46.3)	76 (31.9)	0.02
Age (yr)	44.9 ± 17.9	41.8 ± 18.2	NS
Height (cm)	164.2 ± 9.3	165.0 ± 8.6	NS
Weight (kg)	59.4 ± 10.3	58.3 ± 10.8	NS
Baseline AST (IU/L)	27.3 ± 16.0	24.4 ± 24.6	NS
Baseline ALT (IU/L)	25.1 ± 13.9	21.2 ± 26.5	NS
Baseline total bilirubin (mg/dL)	0.6 ± 0.3	0.5 ± 0.2	NS

Values are presented as number (%) or mean± standard deviation.

ATD, antituberculosis drugs; ALT, alanine aminotransferase; AST, aspartate aminotransferase; NS, not significant.

Table 3

Comparisons of the genotype frequencies between ATD-induced liver injury and ATD-tolerant controls

Gene	SNP	rs number	Genotype	ATD-induced liver injury (n = 80)	ATD-tolerant controls (n = 238)	P-value
IL10	−1082A > G	rs1800896	AA	72 (90.0)	210/237 (88.6)	NS
			GA	8 (10.0)	27/237 (11.4)
			GG	0 (0)	0/237 (0)
	−819T > C	rs1800871	TT	38 (47.5)	124/235 (52.8)	NS
			TC	36 (45.0)	101/235 (43.0)
			CC	6 (7.5)	10/235 (4.2)
TGFB1	−509C > T	rs1800469	TT	18 (22.5)	68/236 (28.8)	NS
			TC	40 (50.0)	112/236 (47.5)
			CC	22 (27.5)	56/236 (23.7)

ATD, antituberculosis drugs; SNP, single nucleotide polymorphism; NS, not significant.

Table 4

Associations of immune related genes with ATD-induced liver injury

Gene	Allele	OR (95% CI)	Ethnicity	Reference
HLA	DQA1^*0102	0.2 (0.05–0.61)	Indian	17
	DQB1^*0201	1.9 (1.19–4.15)	Indian	17
	DQB1^05/^05	5.28 (1.1–24.61)	Chinese	18
TNFA	−308A	1.95 (1.11–3.44)	Korean	12
STAT3	haplotype GAT	12.38 (6.40–23.93)	Chinese	19
STAT3	haplotype AGC	20.81 (5.64–76.70)	Chinese	19

ATD, antituberculosis drugs; OR, odds ratio; CI, confidence interval; HLA, human leukocyte antigen.

Notes

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI15C1234).

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ORCID iDs: Sang-Heon Kim
https://orcid.org/http://orcid.org/0000-0001-8398-4444
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