Association of N-acetyltransferase 2 (NAT2) polymorphisms and elevated liver enzymes of Myanmar TB patients in Thailand

Abstract

Isoniazid (INH) and its toxic metabolites are the major cause of anti-tuberculosis drug-induced liver injury (AT-DILI). N-acetyltransferase 2 (NAT2) is involved in many metabolic pathways of INH. Previous studies demonstrated the association of NAT2 polymorphisms and AT-DILI. This study aimed to determine NAT2 gene polymorphisms in Myanmar TB patients and evaluate the association of NAT2 polymorphisms with elevated liver enzymes. In 59 patients, the most common alleles and genotypes were NAT2*6A and NAT2*4/*7B. A high ratio of slow acetylators (47%, n=28) and intermediate acetylators (44%, n=26) was observed. The CT genotype of NAT2 SNP rs1799929 was frequently observed in patients with elevated AST levels. Slow acetylators with NAT2*5B/*5B showed the highest AST and ALT levels. Multiple linear regression showed the significant association of NAT2 SNP rs1799929, isoniazid dose, and age with variation of AST levels (R2=0.356), while NAT2 phenotype, isoniazid dose, and age linked with variation of AST levels (R2=0.222). NAT2 SNP rs1799929 also exhibited 22% of ALT level variation. The NAT2 genotype and phenotype distribution in the Myanmar population are similar to those in other Southeast Asian populations. A strong influence of NAT2 polymorphisms on elevated liver enzymes suggests closely monitoring of AT-DILI in Myanmar TB patients.