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Chinese Journal of Antituberculosis ›› 2013, Vol. 35 ›› Issue (3): 179-182.

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The relationship between N-acetyltransferase 2 genotypes and the concentration of isoniazid in human plasma

LIU Cheng-cheng, JIN Hai-xia, XU Jian, LI Hua, ZHU Hui, FU Lei, WANG Bin, LU Yu   

  1. Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Department of Pharmacology, Beijing 101149, China
  • Received:2012-12-07 Online:2013-03-10 Published:2013-03-14
  • Contact: LU Yu E-mail:luyu4876@hotmail.com

Abstract: Objective To study the correlation between N-acetyltransferase 2 (NAT2) genotypes and the concentration of isoniazid (INH) in the plasma, and provide a theoretical basis for the individualized medication of tuberculosis (TB) patients by NAT2 genotyping. Methods The NAT2 genotypes of 121 TB patients were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). INH concentration in the plasma was detected by the liquid chromatography-tandem mass spectrometry (LC/MS-MS) at 2 hours after treatment. The differences between the groups were tested by using single factor analysis of variance, and then the differences of every two groups were tested by using Tamhane’s T2, P<0.05 was considered statistically significant.  Results Of 121 TB patients, 55 were NAT2 rapid acetylation (RA) type,and their average concentration of INH in plasma was(1.86±1.28)μg/ml; 17 were slow acetylation (SA) type (homozygous mutant), their INH concentration was(5.86±2.10)μg/ml; 49 were intermediate acetylation (IA) type (heterozygous mutant), and the INH concentration was(3.49±2.60)μg/ml. INH concentration of hospitalized TB patients in plasma was(3.08±2.42)μg/ml. INH concentration among the three groups have statistically significant differences (RA with IA, P=0.001;RA with SA,P=0.002; IA with SA,P=0.000,P<0.05).  Conclusion There were significant differences among the TB patients with different NAT2 genotypes. NAT2 genotyping has important guiding significance for the INH treatment in the TB patients.

Key words: Tuberculosis, pulmonary, Arylamine N-acetyltransferase, Isoniazid, Genotype, Plasma concentration