Worldwide distribution of NAT2 diversity: Implications for NAT2 evolutionary history

Abstract

Background: The N-acetyltransferase 2 (NAT2) gene plays a crucial role in the metabolism of many drugs and xenobiotics. As it represents a likely target of population-specific selection pressures, we fully sequenced the NAT2 coding region in 97 Mandenka individuals from Senegal, and compared these sequences to extant data on other African populations. The Mandenka data were further included in a worldwide dataset composed of 41 published population samples (6,727 individuals) from four continental regions that were adequately genotyped for all common NAT2 variants so as to provide further insights into the worldwide haplotype diversity and population structure at NAT2.

Arylamine N-acetyltransferase 2 genotypes in a Mexican population

“…In an attempt to better characterize the worldwide haplotype diversity and structure of NAT2, Sabbagh et al (2008) reported the results of 41 population samples (including 6727 individuals) from four continental regions (Africa, Europe, Asia, America). Our results were compared with data for each of these populations and showed statistically significant differences with all but the Turkish population.…”

Comparative genomic and phylogenetic investigation of the xenobiotic metabolizing arylamine N‐acetyltransferase enzyme family

“…Initial searches were performed by tBLASTn, using the protein sequences of: (a) Salmonella typhimurium NAT1 4,5 in order to update our previous catalogues of annotated NAT genes for these taxonomic groups [8]. The genomes of archaea, 1,4 protists 2,5 and fungi 2,3,5 were each one interrogated separately. Conventional (nBLAST) and tBLASTn queries of the GenBank complete nucleotide collection (nr/nt), as well as of the whole-genome shotgun and expressed sequence tag (EST) databases were additionally performed.…”

The distribution of allelic and genotypic frequencies of N-Acetyltransferase-2 variants in an Argentine population

“…Expected genotype frequencies were calculated from respective single allele frequencies and were consistent with Hardy Weinberg equilibrium. Table 1 describes the allelic distribution of the four variants of NAT-2 that had the strongest impact on the acetylation profile in the Buenos Aires population and in different populations from various regions of Europe [1], Africa [1,12], Asia [1,6,9] and America [1,7 ,9, 13]. Our study group consisted of an admixture of ethnic groups with European (mainly from Spain, Italy and, to a lesser extent, from Germany and other countries of Eastern Europe), and Native American ancestries.…”

“…Arylamine N-acetyltransferase-2 (NAT-2) is a cytosolic phase II conjugation enzyme that plays a key role in the detoxification and elimination of many commonly prescribed drugs through acetylation, and it is also involved in the metabolism of carcinogens from environmental, industrial and dietary sources [1]. NAT-2 is a highly polymorphic enzyme.…”

“…The SA acetylation status has been associated with Isoniazid (INH)-induced hepatitis in Asian populations [1,5]. INH, a substrate of NAT-2, is a first-line drug used in tuberculosis (TB) treatment, and it is considered to be responsible for adverse drug reactions that lead to hepatotoxicity [6,8,9].…”