Association of Drug Metabolic Enzyme Genetic Polymorphisms and Adverse Drug Reactions in Patients Receiving Rifapentine and Isoniazid Therapy for Latent Tuberculosis

Ya-Yen Yu; Shih-Ming Tsao; Wen-Ta Yang; Wei-Chang Huang; Ching-Hsiung Lin; Wei-Wen Chen; Shun-Fa Yang; Hui-Ling Chiou; Yi-Wen Huang

doi:10.3390/ijerph17010210

Association of Drug Metabolic Enzyme Genetic Polymorphisms and Adverse Drug Reactions in Patients Receiving Rifapentine and Isoniazid Therapy for Latent Tuberculosis

Int J Environ Res Public Health. 2019 Dec 27;17(1):210. doi: 10.3390/ijerph17010210.

Authors

Ya-Yen Yu^{1

2}, Shih-Ming Tsao^{3

4}, Wen-Ta Yang⁵, Wei-Chang Huang^{6

7

8

9}, Ching-Hsiung Lin¹⁰, Wei-Wen Chen¹¹, Shun-Fa Yang^{1

12}, Hui-Ling Chiou^{13

14}, Yi-Wen Huang^{1

11}

Affiliations

¹ Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
² Department of Clinical Laboratory, Changhua Hospital, Changhua 513, Taiwan.
³ Division of Chest, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
⁴ Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 402, Taiwan.
⁵ Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung 403, Taiwan.
⁶ Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan.
⁷ Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 356, Taiwan.
⁸ Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.
⁹ Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung 407, Taiwan.
¹⁰ Division of Chest, Changhua Christian Hospital, Changhua 500, Taiwan.
¹¹ Department of Health, Pulmonary and Critical Care Unit, Changhua Hospital, Changhua 500, Taiwan.
¹² Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
¹³ School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan.
¹⁴ Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan.

Abstract

Weekly rifapentine and isoniazid therapy (3HP) is the most frequent treatment for latent tuberculosis infection (LTBI). However, the association between major adverse drug reactions (ADRs) and drug metabolic enzyme single-nucleotide polymorphisms (SNPs) remains unclear. In this study, 377 participants who received the 3HP regimen were recruited and examined for genotyping of CYP5A6, CYP2B6, CYP2C19, CYP2E1, and NAT2 SNPs. In our study, 184 participants (48.4%) developed ADRs. Moreover, CYP2C19 rs4986893 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 2.231 [1.015-4.906]), CYP2E1 rs2070676 (CC vs. CG+GG, OR [95% CI]: 1.563 [1.022-2.389]), and CYP2E1 rs2515641 (CC vs. CT+TT, OR [95% CI]: 1.903 [1.250-2.898]) were associated with ADR development. In conclusion, CYP2C19 and CYP2E1 SNPs may provide useful information regarding ADRs in LTBI patients receiving the 3HP regimen.

Keywords: adverse drug reaction; drug metabolic enzymes; latent tuberculosis; polymorphism.

MeSH terms

Adult
Antitubercular Agents / administration & dosage
Antitubercular Agents / adverse effects
Antitubercular Agents / therapeutic use*
Arylamine N-Acetyltransferase / genetics*
Cytochrome P-450 Enzyme System / genetics*
Drug Administration Schedule
Drug Therapy, Combination
Drug-Related Side Effects and Adverse Reactions
Female
Humans
Isoniazid / administration & dosage
Isoniazid / adverse effects
Isoniazid / therapeutic use*
Latent Tuberculosis / drug therapy*
Male
Odds Ratio
Polymorphism, Single Nucleotide*
Rifampin / administration & dosage
Rifampin / adverse effects
Rifampin / analogs & derivatives*
Rifampin / therapeutic use

Substances

Antitubercular Agents
Cytochrome P-450 Enzyme System
Arylamine N-Acetyltransferase
NAT2 protein, human
Isoniazid
Rifampin
rifapentine