Genotype and phenotype of NAT2 and the occurrence of adverse drug reactions in Mexican individuals to an isoniazid-based prophylactic chemotherapy for tuberculosis.

ABSTRACT

Isoniazid (INH) is a drug extensively used as a prophylactic and therapeutic agent for human tuberculosis (TB). INH is metabolized by the enzymatic activity of N-acetyltransferase 2 (NAT2). Human NAT2, encoded by a highly polymorphic gene, is involved in the biotransformation of xenobiotics, including drugs and certain chemical carcinogens. Numerous studies have established the correlation between the acetylator phenotype and the NAT2 genotype in several populations; however, little is known regarding Latin-American populations and the pharmacogenetics of NAT2. Here, we report the molecular genotyping of the NAT2 gene, the acetylator phenotype, and the incidence of INH-related adverse reactions in a group of 25 Mexican individuals enrolled in a prophylactic protocol for TB. Using both the NAT2 genotyping and acetylation phenotyping approach, we found a ratio of 69.2 and 30.8% of slow and fast acetylators, respectively. Concordance of the NAT2 genotype and phenotype classification was 88% in the bimodal model. Regarding INH-related adverse reactions, only 2 individuals (8%) exhibited declared gastric intolerance. In our study group, we found an association between the NAT2 genotype and acetylator phenotype (OR=7.78, 95% CI, 0.87-87.98, Fisher's exact test, p<0.05), but did not find any genotype or phenotype association with the incidence of INH-related adverse reactions (Fisher's exact test, p>0.05).