Won Yong Suh; Yo Han Kim; Hyun Don Joo; Seong Jun Park; Sung Hyeok Ryuo; Ji Sung Choi; Sun Young Ann; Chang Hyun Park; Sang-Hoon Kim; Sang-Heon Kim; Young-Koo Jee

doi:10.4168/aard.2015.3.2.124

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Suh, Kim, Joo, Park, Ryuo, Choi, Ann, Park, Kim, Kim, and Jee: Lack of associations between tumor necrosis factor-α genetic polymorphism -308G/A and antituberculous drug-induced maculopapular eruption

Original Article

Allergy, Asthma & Respiratory Disease 2015; 3(2): 124-127.

Published online: 24 March 2015

DOI: https://doi.org/10.4168/aard.2015.3.2.124

Lack of associations between tumor necrosis factor-α genetic polymorphism -308G/A and antituberculous drug-induced maculopapular eruption

Won Yong Suh¹, Yo Han Kim¹, Hyun Don Joo¹, Seong Jun Park¹, Sung Hyeok Ryuo¹, Ji Sung Choi¹, Sun Young Ann¹, Chang Hyun Park¹, Sang-Hoon Kim², Sang-Heon Kim³, Young-Koo Jee¹

¹Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.

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

³Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.

Correspondence to: Young-Koo Jee. Department of Internal Medicine, Dankook University College of Medicine, 119 Dandae-ro, Dongnam-gu, Cheonan 330-997, Korea. Tel: +82-41-550-3923, Fax: +82-41-556-3256, ykjee@dankook.ac.kr

Received 1 September 2014 Revised 2 September 2014 Accepted 12 September 2014

(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/3.0/).

Abstract

Purpose

Adverse cutaneous reactions to antituberculous drugs (ATD), such as maculopapular eruption (MPE), are the most common causes of discontinuation of scheduled treatment of tuberculosis. We previously reported that tumor necrosis factor (TNF)-α genetic polymorphism -308G/A is significantly associated with ATD-induced hepatitis. This study aimed to investigate associations between TNF-α -308G/A and ATD-induced MPE.

Methods

Patients with ATD-induced MPE and controls without any adverse reactions to ATD were recruited from the database of the Adverse Drug Reaction Pharmacogenomic Research Group database of Korea. We compared the genotype frequency of TNF-α-308G/A between patients with ATD-induced MPE and ATD-tolerant controls.

Results

A total of 69 patients with ATD-induced MPE and 229 control subjects were enrolled for this study. There were no significant differences in genotype frequency between the patients and the controls, suggesting lack of associations between TNF-α-308G/A and ATD-induced MPE.

Conclusion

The TNF-α genetic polymorphism -308G/A may not be related to the development of ATD-induced MPE, in contrast to ATD-induced hepatitis. These findings suggest that associations between TNF-α-308G/A and ATD-induced adverse reactions can be phenotype-specific.

Keywords: Genetic polymorphism, Tumor necrosis factor-alpha, Antitubercular agents, Drug eruption

Figures and Tables

Table 1

Clinical characteristics of the study subjects

Characteristic	ATD-induced MPE (n = 69)	ATD-tolerant (n = 229)	P-value
Male sex	57.9 (40)	67.7 (155)	NS
Age (yr)	48.3 ± 18.9	43.1 ± 17.0	NS
Height (cm)	161.6 ± 9.8	165.5 ± 8.9	NS
Weight (kg)	58.0 ± 10.6	58.1 ± 10.7	NS
Baseline AST (U/mL)	21.6 ± 8.8	24.4 ± 24.6	NS
Baseline ALT (U/mL)	19.4 ± 11.7	21.2 ± 26.5	NS
Baseline bilirubin (mg/dL)	0.5 ± 0.2	0.5 ± 0.2	NS

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

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

Table 2

TNF-α polymorphism -308G/A in patents with ATD-induced MPE and ATD-tolerant controls

Genotype	ATD-induced MPE (n = 69)	ATD-tolerant (n = 229)	P-value	OR (95% CI)
GG	57 (82.6%)	194 (84.7%)	0.718^*	1.14 (0.55-2.38)^*
AG	12 (17.4%)	34 (14.9%)	-	-
AA	0 (0%)	1 (0.4%)	-	-
A allele	0.087	0.079	0.784	1.10 (0.56-2.21)

TNF, tumor necrosis factor; ATD, antituberculosis drugs; MPE, maculopapular eruption; OR, odds ratio; CI, confidence interval.

^*Statistical analysis was performed with dominant model (AG + AA vs. GG).

Notes

This research was supported by a grant of Korea Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), founded by the Ministry of Health & Welfare, Republic of Korea (grant No. HI14C0065).

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ORCID iDs: Young-Koo Jee
https://orcid.org/http://orcid.org/0000-0001-5800-8038
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