A web server for inferring the human N-acetyltransferase-2 (NAT2) enzymatic phenotype from NAT2 genotype

Gen*NY*Sis Center for Excellence in Cancer Genomics, Department of Epidemiology and Biostatistics, University at Albany, One Discovery Drive, Rensselaer, NY 12144, USA.
Bioinformatics (Impact Factor: 4.98). 04/2009; 25(9):1185-6. DOI: 10.1093/bioinformatics/btp121
Source: PubMed


N-acetyltransferase-2 (NAT2) is an important enzyme that catalyzes the acetylation of aromatic and heterocyclic amine carcinogens. Individuals in human populations are divided into three NAT2 acetylator phenotypes: slow, rapid and intermediate. NAT2PRED is a web server that implements a supervised pattern recognition method to infer NAT2 phenotype from SNPs found in NAT2 gene positions 282, 341, 481, 590, 803 and 857. The web server can be used for a fast determination of NAT2 phenotypes in genetic screens.
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Supplementary information:Supplementary data are available at Bioinformatics online.

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    • "However, recently a common tag SNP (rs1495741) and seven SNPs (rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208 and rs1799931) were found to be highly relevant with slow acetylation phenotypes. The latest contributions to related work is genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) that outperforms the tagging SNP and is equivalent to the conventional 7-SNP NAT2 genotyping strategy in determining the acetylation status (Kuznetsov et al., 2009; Garcia-Closas and Hein, 2011; Selinski et al., 2011). rs1801280 is found to be the signature SNP for 16 over 68 haplotype clusters. "
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    ABSTRACT: Genotyping N-acetyltransferase 2 (NAT2) for acetylation status of its enzyme is very important for personalized medicine, especially individualized dosing of anti-tuberculosis drugs and in bladder cancer epidemiology. Human NAT2 gene with at least 359 single nucleotide polymorphism (SNP) accessions is highly polymorphic which makes it difficult to design specific primers for allele specific PCR. Because of this, sequencing is the preferred choice to genotype for NAT2. Currently, a common tag SNP (rs1495741) and 7 SNPs (rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208 and rs1799931) are found to be highly relevant with slow acetylation phenotypes. One of the latest contributions to related work is genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) that outperforms the tagging SNP and is equivalent to the conventional 7-SNP NAT2 genotyping strategy. The aim of our work is to decrease the number of samples to be sequenced for one of the aforementioned SNPs (rs1801280 341T>C) using high-resolution melting analysis sequence matching function. It enables a prior elimination of the samples to be sequenced that are above a user-defined confidence threshold when genotypes are auto-called in comparison with sequencing and KASP confirmed reference samples. The workflow in screening type 1 SNP (341T>C) was shown with various remarks to experimental flow, such as improving the usability by gradient facility of thermal cyclers, HRM availability of Rotor-Gene 6000™ real-time PCR instrument and its software with auto-calling genotypes function, the commercially available EvaGreen™ based HRM kits and challenges of method.
    Full-text · Article · Jun 2012 · African journal of pharmacy and pharmacology
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    • "To circumvent these limitations, Kuznetsov et al. [10] have developed a web-server NAT2PRED that allows a fast determination of NAT2 acetylation phenotypes (slow, intermediate, and rapid) from the unphased genotype data at six polymorphic positions in NAT2. These six SNPs are the most commonly reported ones in surveys of NAT2 sequence variation in human populations [11]. "
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    ABSTRACT: Genetically determined differences in N-acetylation capacity have proved to be important determinants of both the effectiveness of therapeutic response and the development of adverse drug reactions and toxicity during drug treatment. NAT2PRED is a web-server that allows a fast determination of NAT2 acetylation phenotype from genotype data without taking the extra step of reconstructing haplotypes for each individual (publicly available at However, the classification accuracy of NAT2PRED needs to be assessed before its application can be advocated at a large scale. The ability of NAT2PRED to classify individuals according to their acetylation status (slow, intermediate and rapid acetylators) was evaluated in a worldwide dataset composed of 56 population samples (8,489 individuals) from four continental regions. NAT2PRED correctly identified slow acetylators with a sensitivity above 99% for all populations outside sub-Saharan Africa. Nevertheless, NAT2PRED showed a poor ability to distinguish between intermediate and rapid acetylators, with a classification error rate reaching up to 10% in the non-African samples. NAT2PRED is an excellent tool to infer the individual acetylation status from NAT2 genotype data when the main interest is to distinguish slow acetylators from the others. This should facilitate the determination of the individual acetylation status in routine clinical practice and lead to better monitoring of risks associated with cancer and adverse drug reactions.
    Full-text · Article · Dec 2009 · BMC Medical Genetics
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    ABSTRACT: N-Acetylation by hepatic arylamine N-acetyltransferase (NAT, EC is a major route in the metabolism and detoxification of numerous drugs and foreign chemicals. NAT is the target of a common genetic polymorphism of clinical relevance in human populations. We have used our recently isolated rabbit cDNA rnat to clone three human NAT genes from human leukocyte DNA. None of the three genomic coding sequences was interrupted by introns. Two genes, designated NAT1 and NAT2, each possessed open reading frames of 870 bp. Both genes have been assigned to human chromosome 8, pter-q11. Following transfection they were transiently expressed in monkey kidney COS-1 cells. NAT1 and NAT2 gave rise to functional NAT proteins, as judged by their NAT enzyme activity with the arylamine substrate sulfamethazine. Western blots with NAT-specific antisera detected proteins of apparent molecular weight of 33 and 31 kD in NAT1- and NAT2-transfected cultures, respectively. The product of NAT2 had an identical apparent molecular weight as that of NAT detected in human liver cytosol. The deduced amino acid sequence of NAT2 also contained 6 peptide sequences which had previously been determined from tryptic peptides of the polymorphic NAT purified from human liver. These data suggest that NAT2 encodes the polymorphic NAT protein. The third gene, NATP, had multiple deleterious mutations and did not encode a functional NAT protein; it most likely represents a pseudogene.
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