Hemanth Kumar A K, Ramesh K, Kannan T, Sudha V, Haribabu Hemalatha, Lavanya J, Swaminathan Soumya, Ramachandran Geetha
Department of Biochemistry & Clinical Pharmacology, ICMR-National Institute for Research in Tuberculosis, Chennai, India.
HIV/AIDS Division, ICMR-National Institute for Research in Tuberculosis, Chennai, India.
Indian J Med Res. 2017 Jan;145(1):118-123. doi: 10.4103/ijmr.IJMR_2013_15.
BACKGROUND & OBJECTIVES: Variations in the N-acetyltransferase (NAT2) gene among different populations could affect the metabolism and disposition of isoniazid (INH). This study was performed to genotype NAT2 gene polymorphisms in tuberculosis (TB) patients from Chennai, India, and compare plasma INH concentrations among the different genotypes.
Adult patients with TB treated in the Revised National TB Control Programme (RNTCP) in Chennai, Tamil Nadu, were genotyped for NAT2 gene polymorphism, and two-hour post-dosing INH concentrations were compared between the different genotypes. Plasma INH was determined by high-performance liquid chromatography. Genotyping of the NAT2 gene polymorphism was performed by real-time polymerase chain reaction method.
Among the 326 patients genotyped, there were 189 (58%), 114 (35%) and 23 (7%) slow, intermediate and fast acetylators, respectively. The median two-hour INH concentrations in slow, intermediate and fast acetylators were 10.2, 8.1 and 4.1 μg/ml, respectively. The differences in INH concentrations among the three genotypes were significant (P<0.001).
INTERPRETATION & CONCLUSIONS: Genotyping of TB patients from south India for NAT2 gene polymorphism revealed that 58 per cent of the study population comprised slow acetylators. Two-hour INH concentrations differed significantly among the three genotypes.
不同人群中N - 乙酰转移酶（NAT2）基因的变异可能影响异烟肼（INH）的代谢和处置。本研究旨在对印度钦奈的结核病（TB）患者进行NAT2基因多态性基因分型，并比较不同基因型之间的血浆INH浓度。
在泰米尔纳德邦钦奈的修订国家结核病控制计划（RNTCP）中接受治疗的成年TB患者进行NAT2基因多态性基因分型，并比较不同基因型给药后两小时的INH浓度。通过高效液相色谱法测定血浆INH。通过实时聚合酶链反应法进行NAT2基因多态性的基因分型。
在进行基因分型的326例患者中，分别有189例（58%）、114例（35%）和23例（7%）为慢乙酰化者、中间乙酰化者和快乙酰化者。慢乙酰化者、中间乙酰化者和快乙酰化者两小时INH浓度的中位数分别为10.2、8.1和4.1μg/ml。三种基因型之间INH浓度的差异具有统计学意义（P<0.001）。
对印度南部TB患者进行NAT2基因多态性基因分型显示，研究人群中有58%为慢乙酰化者。三种基因型之间两小时INH浓度差异显著。
