ArticlePharmacogenetics and genomics2007
Functional characterization of the A411T (L137F) and G364A (D122N) genetic polymorphisms in human N-acetyltransferase 2.
Article in Pharmacogenetics and genomics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 28 citations in OpenAlex.
- The actinobacterium Tsukamurella paurometabola has a functionally divergent arylamine N-acetyltransferase (NAT) homolog.World journal of microbiology & biotechnology · 2019Article
- Comparative analysis of xenobiotic metabolising N-acetyltransferases from ten non-human primates as in vitro models of human homologues.Scientific reports · 2018Article
- Xenobiotic-metabolizing enzymes in Bacillus anthracis: molecular and functional analysis of a truncated arylamine N-acetyltransferase isozyme.British journal of pharmacology · 2017Article
- NAT2 variants are associated with drug-induced liver injury caused by anti-tuberculosis drugs in Indonesian patients with tuberculosis.Journal of human genetics · 2016Article
- Structural and biochemical characterization of an active arylamine N-acetyltransferase possessing a non-canonical Cys-His-Glu catalytic triad.The Journal of biological chemistry · 2013Article
- Purification, crystallization and preliminary X-ray characterization of Bacillus cereus arylamine N-acetyltransferase 3 [(BACCR)NAT3].Acta crystallographica. Section F, Structural biology and crystallization communications · 2012Article
- Effects of single nucleotide polymorphisms on human N-acetyltransferase 2 structure and dynamics by molecular dynamics simulation.PloS one · 2011Article
- N-acetyltransferase SNPs: emerging concepts serve as a paradigm for understanding complexities of personalized medicine.Expert opinion on drug metabolism & toxicology · 2009Review
- Functional effects of single nucleotide polymorphisms in the coding region of human N-acetyltransferase 1.The pharmacogenomics journal · 2008Article
- Structure/function evaluations of single nucleotide polymorphisms in human N-acetyltransferase 2.Current drug metabolism · 2008Review
- Functional characterization of single-nucleotide polymorphisms and haplotypes of human N-acetyltransferase 2.Carcinogenesis · 2007Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectivesHuman N-acetyltransferase 2 (NAT2) genetic polymorphisms may modify drug efficacy and toxicity and cancer susceptibility from carcinogen exposure. Two human NAT2 alleles, NAT2*5I and NAT2*12D, were identified recently. In NAT2*5I, a new single nucleotide polymorphism AT (L137F) was found coexisting with single nucleotide polymorphisms TC (I114T), CT (silent) and AG (K268R). The other allele NAT2*12D consists of a new single nucleotide polymorphism GA (D122N) together with AG (K268R). We undertook a study to characterize these new single nucleotide polymorphisms and NAT2 alleles to further our understanding of genotype/phenotype relationships in human populations.
methodsVarious human NAT2 alleles were cloned and recombinantly expressed in COS-1 cells and the effects of single nucleotide polymorphisms on NAT2 expression were determined. To further test our hypothesis that AT (L137F) and GA (D122N) accelerate protein degradation, various NAT2 alleles were cloned and expressed in Escherichia coli, which does not possess the ubiquitin-mediated degradation pathway.
resultsBoth AT and GA reduced NAT2 immuno-reactive protein to an undetectable level without causing changes in mRNA level. Missense mutants displayed different effects on sulfamethazine N-acetylation activity for both L137 (wild-type: 70.2+/-5.2 nmol/min/mg; L137F: 1.34+/-0.03 nmol/min/mg; L137W: nondetectable; L137I: 34.2+/-2.0 nmol/min/mg; L137G: 0.52+/-0.04 nmol/min/mg) and D122 (wild-type: 70.2+/-5.2 nmol/min/mg; D122R: non-detectable; D122Q: non-detectable; D122E: 1.72+/-0.24 nmol/min/mg). In contrast to the expression in mammalian cells, recombinant NAT2 possessing either of these two single nucleotide polymorphisms showed no reduction in immuno-reactive NAT2 level when expressed in E. coli.
conclusionsThese findings suggest that both AT (L137F) and GA (D122N) enhance NAT2 degradation, resulting in reduced NAT2 protein and catalytic activity for NAT2 5I and NAT2 12D.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.