ArticlePharmacogenetics and genomics2011
Human N-acetyltransferase 1 *10 and *11 alleles increase protein expression through distinct mechanisms and associate with sulfamethoxazole-induced hypersensitivity.
Article in Pharmacogenetics and genomics, 2011. 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.
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
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Safety of sulfamethoxazole-trimethoprim for the treatment of bacterial infection in outpatient settings: A systematic review and meta-analysis with active comparator disproportionality analysis.British journal of clinical pharmacology · 2025Pooled it
- Safety of sulfamethoxazole-trimethoprim for the treatment of bacterial infection in outpatient settings: A systematic review and meta-analysis with active comparator disproportionality analysis.British journal of clinical pharmacology · 2025Pooled it
- Suboptimal cotrimoxazole prophylactic concentrations in HIV-infected children according to the WHO guidelines.British journal of clinical pharmacology · 2017Trial
- Regulation of NAT1 activity in modern humans by a novel phosphorylation site.Science advances · 2026Article
- N-acetyltransferase (NAT) 1 and NAT2 enzyme activities drive interindividual variability in sulfamethoxazole N-acetylation.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Characterization of NAT, GST, and CYP2E1 Genetic Variation in Sub-Saharan African Populations: Implications for Treatment of Tuberculosis and Other Diseases.Clinical pharmacology and therapeutics · 2025Article
- Pharmacogenomics of Allopurinol and Sulfamethoxazole/Trimethoprim: Case Series and Review of the Literature.Journal of personalized medicine · 2021Article
- Interactions Between Regulatory Variants in CYP7A1 (Cholesterol 7α-Hydroxylase) Promoter and Enhancer Regions Regulate CYP7A1 Expression.Circulation. Genomic and precision medicine · 2018Article
- Functional expression of human arylamine N-acetyltransferase NAT1*10 and NAT1*11 alleles: a mini review.Pharmacogenetics and genomics · 2018Review
- Trimodal distribution of arylamine N-acetyltransferase 1 mRNA in breast cancer tumors: association with overall survival and drug resistance.BMC genomics · 2018Article
- Article
- Article
- Variation in NAT2 acetylation phenotypes is associated with differences in food-producing subsistence modes and ecoregions in Africa.BMC evolutionary biology · 2015Article
- NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study.BMC cancer · 2015Article
- Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms.PloS one · 2015Article
- Arylamine N-acetyltransferase polymorphisms in Han Chinese patients with ankylosing spondylitis and their correlation to the adverse drug reactions to sulfasalazine.BMC pharmacology & toxicology · 2014Article
- Missing heritability of common diseases and treatments outside the protein-coding exome.Human genetics · 2014Review
- Pharmacogenomics of antimicrobial agents.Pharmacogenomics · 2014Review
- Common CYP2D6 polymorphisms affecting alternative splicing and transcription: long-range haplotypes with two regulatory variants modulate CYP2D6 activity.Human molecular genetics · 2014Article
- Whole transcriptome RNA-Seq allelic expression in human brain.BMC genomics · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesN-acetyltransferase 1 (NAT1) metabolizes drugs and environmental carcinogens. NAT1 alleles *10 and *11 have been proposed to alter protein level or enzyme activity compared with wild-type NAT1 *4 and to confer cancer risk, through uncertain pathways. This study characterizes regulatory polymorphisms and underlying mechanisms of NAT1 expression.
methodsWe measured allelic NAT1 mRNA expression and translation, as a function of multiple transcription start sites, alternative splicing, and three 3'-polyadenylation sites in human livers (one of which was discovered in this study), B lymphocytes, and transfected cells. In a clinical study of 469 patients with HIV/AIDS treated with the NAT1/NAT2 substrate sulfamethoxazole (SMX), associations were tested between SMX-induced hypersensitivity and NAT1 *10 and *11 genotypes, together with known NAT2 polymorphisms.
resultsNAT1 *10 and *11 were determined to act as common regulatory alleles accounting for most NAT1 expression variability, both leading to increased translation into active protein. NAT1 *11 (2.4% minor allele frequency) affected 3'-polyadenylation site usage, thereby increasing formation of NAT1 mRNA with intermediate length 3'-untranslated region (major isoform) at the expense of the short isoform, resulting in more efficient protein translation. NAT1 *10 (19% minor allele frequency) increased translation efficiency without affecting 3'-untranslated region polyadenylation site usage. Livers and B-lymphocytes with *11/*4 and *10/*10 genotypes displayed higher NAT1 immunoreactivity and NAT1 enzyme activity than the reference genotype *4/*4. Patients who carry *10/*10 and *11/*4 (fast NAT1 acetylators) were less likely to develop hypersensitivity to SMX, but this was observed only in individuals who are also carrying a slow NAT2 acetylator genotype.
conclusionNAT1 *10 and *11 significantly increase NAT1 protein level/enzyme activity, enabling the classification of carriers into reference and rapid acetylators. Rapid NAT1 acetylator status seems to protect against SMX toxicity by compensating for slow NAT2 acetylator status.
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.