ArticlePloS one2008
Multiple advantageous amino acid variants in the NAT2 gene in human populations.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- NAT2 global landscape: Genetic diversity and acetylation statuses from a systematic review.PloS one · 2023Pooled it
- Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene.The Journal of clinical investigation · 2015Pooled it
- Comparative evolutionary and structural bioinformatic analysis of the human N-Acetyltransferase-2 (NAT2) gene with different mammalian and avian taxa.BMC genomics · 2026Article
- Genomic diversity and structure of prehistoric alpine individuals from the Tyrolean Iceman's territory.Nature communications · 2025Article
- Clinical Significance of NAT2 Genetic Variations in Type II Diabetes Mellitus and Lipid Regulation.Pharmacogenomics and personalized medicine · 2023Article
- THE EXPOSOME IN HUMAN EVOLUTION: FROM DUST TO DIESEL.The Quarterly review of biology · 2019Article
- Beyond drugs: the evolution of genes involved in human response to medications.Proceedings. Biological sciences · 2019Article
- Genetics, adaptation to environmental changes and archaic admixture in the pathogenesis of diabetes mellitus in Indigenous Australians.Reviews in endocrine & metabolic disorders · 2019Review
- Population variability of rhesus macaque (Macaca mulatta) NAT1 gene for arylamine N-acetyltransferase 1: Functional effects and comparison with human.Scientific reports · 2019Article
- Humans and Chimpanzees Display Opposite Patterns of Diversity inG3 (Bethesda, Md.) · 2019Article
- FADS1 and the Timing of Human Adaptation to Agriculture.Molecular biology and evolution · 2018Article
- N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians.European journal of clinical pharmacology · 2018Article
- Comparative analysis of xenobiotic metabolising N-acetyltransferases from ten non-human primates as in vitro models of human homologues.Scientific reports · 2018Article
- Variation in NAT2 acetylation phenotypes is associated with differences in food-producing subsistence modes and ecoregions in Africa.BMC evolutionary biology · 2015Article
- Exploring the relationship between lifestyles, diets and genetic adaptations in humans.BMC genetics · 2015Article
- Haplotype differences for copy number variants in the 22q11.23 region among human populations: a pigmentation-based model for selective pressure.European journal of human genetics : EJHG · 2015Article
- PharmGKB summary: very important pharmacogene information for N-acetyltransferase 2.Pharmacogenetics and genomics · 2014Review
- NAT2 genetic variations among South Indian populations.Human genome variation · 2014Article
- Rapid birth-and-death evolution of the xenobiotic metabolizing NAT gene family in vertebrates with evidence of adaptive selection.BMC evolutionary biology · 2013Article
- Characterization of genetic variation and natural selection at the arylamine N-acetyltransferase genes in global human populations.Pharmacogenomics · 2011Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic variation at NAT2 has been long recognized as the cause of differential ability to metabolize a wide variety of drugs of therapeutic use. Here, we explore the pattern of genetic variation in 12 human populations that significantly extend the geographic range and resolution of previous surveys, to test the hypothesis that different dietary regimens and lifestyles may explain inter-population differences in NAT2 variation. METHODOLOGY/PRINCIPAL
findingsThe entire coding region was resequenced in 98 subjects and six polymorphic positions were genotyped in 150 additional subjects. A single previously undescribed variant was found (34T>C; 12Y>H). Several aspects of the data do not fit the expectations of a neutral model, as assessed by coalescent simulations. Tajima's D is positive in all populations, indicating an excess of intermediate alleles. The level of between-population differentiation is low, and is mainly accounted for by the proportion of fast vs. slow acetylators. However, haplotype frequencies significantly differ across groups of populations with different subsistence. CONCLUSIONS/SIGNIFICANCE: Data on the structure of haplotypes and their frequencies are compatible with a model in which slow-causing variants were present in widely dispersed populations before major shifts to pastoralism and/or agriculture. In this model, slow-causing mutations gained a selective advantage in populations shifting from hunting-gathering to pastoralism/agriculture. We suggest the diminished dietary availability of folates resulting from the nutritional shift, as the possible cause of the fitness increase associated to haplotypes carrying mutations that reduce enzymatic activity.
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