A simple test for acetylator phenotype using caffeine.

Grant, D M; Tang, Boyu; Kalow, W.

doi:10.1111/j.1365-2125.1984.tb02372.x

Cited by 186 publications

(52 citation statements)

References 16 publications

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“…Although less commonly reported, trimodal (rapid, intermediate and slow acetylator phenotype) distributions of N -acetylation capacity in vivo have been reported in humans following administrations of SMZ [21,22], isoniazid [23–26], sulfasalazine [27] and caffeine [28–29]. …”

Section: Discussionmentioning

confidence: 99%

Accuracy of Various Human NAT2 SNP Genotyping Panels to Infer Rapid, Intermediate and Slow Acetylator Phenotypes

Hein¹,

2011

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Aim Humans exhibit genetic polymorphism in NAT2 resulting in rapid, intermediate and slow acetylator phenotypes. Over 65 NAT2 variants possessing one or more SNPs in the 870-bp NAT2 coding region have been reported. The seven most frequent SNPs are rs1801279 (191G>A), rs1041983 (282C>T), rs1801280 (341T>C), rs1799929 (481C>T), rs1799930 (590G>A), rs1208 (803A>G) and rs1799931 (857G>A). The majority of studies investigate the NAT2 genotype assay for three SNPs: 481C>T, 590G>A and 857G>A. A tag-SNP (rs1495741) recently identified in a genome-wide association study has also been proposed as a biomarker for the NAT2 phenotype. Materials & methods Sulfamethazine N-acetyltransferase catalytic activities were measured in cryopreserved human hepatocytes from a convenience sample of individuals in the USA with an ethnic frequency similar to the 2010 US population census. These activities were segregated by the tag-SNP rs1495741 and each of the seven SNPs described above. We assessed the accuracy of the tag-SNP and various two-, three-, four- and seven-SNP genotyping panels for their ability to accurately infer NAT2 phenotype. Results The accuracy of the various NAT2 SNP genotype panels to infer NAT2 phenotype were as follows: seven-SNP: 98.4%; tag-SNP: 77.7%; two-SNP: 96.1%; three-SNP: 92.2%; and four-SNP: 98.4%. Conclusion A NAT2 four-SNP genotype panel of rs1801279 (191G>A), rs1801280 (341T>C), rs1799930 (590G>A) and rs1799931 (857G>A) infers NAT2 acetylator phenotype with high accuracy, and is recommended over the tag-, two-, three- and (for economy of scale) the seven-SNP genotyping panels, particularly in populations of non-European ancestry.

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Section: Discussionmentioning

confidence: 99%

Accuracy of Various Human NAT2 SNP Genotyping Panels to Infer Rapid, Intermediate and Slow Acetylator Phenotypes

Hein¹,

2011

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“…Caffeine can be used as a non-toxic probe drug in vivo for predicting acetylator phenotype; by measuring metabolite ratio AFMU/1-methyl xanthine (1X) in urine after caffeine consumption, a bi- or tri-modal pattern in a given population is observed [39, 115, 151]. AFMU/AFMU+1X+1-methyluric acid (1U), AFMU+5-acetylamino-6-amino-3-methyluracil (AAMU)/AFMU+AAMU+1X+1U or AAMU/ AAMU+1X+1U metabolite ratios can also be used to determine acetylator phenotype [152–156].…”

Section: Pharmacogeneticsmentioning

confidence: 99%

PharmGKB summary

McDonagh¹,

Boukouvala

Aklillu

et al. 2014

Pharmacogenetics and Genomics

115

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“…26 Designation of the acetylator (NAT2) phenotype was based on the ratio between 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1X). Results showed a clear bimodality of N-acetylation capacity with a ratio cut off point of 1.7 resulting in 61% slow and 39% fast acetylators.…”

Section: Ambient Exposure Measuresmentioning

confidence: 99%

Exposure related mutagens in urine of rubber workers associated with inhalable particulate and dermal exposure

Vermeulen

Bos²,

Pertijs³

et al. 2003

Occup Environ Med

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Aims: To determine the relation of the inhalation and dermal exposure routes and mutagenic activity in the urine of rubber workers (n = 105). Methods: Mutagenic activity of ambient total suspended particulate matter (TSPM), surface contamination wipes, and Sunday and weekday urine samples was assessed with S typhimurium YG1041 in the presence of a metabolic activation system. Each subject was grouped into one of two exposure categories for dermal exposure (high (>25 revertants/cm 2 ), low (<25 revertants/cm 2 )) based on the mutagenic activity detected on likely skin contact surfaces and into two airborne mutagenic exposure categories (high (>210 revertants/m 3 ), low (<210 revertants/m 3 )). The potential influence of skin aberrations and acetylation status (NAT2) on urinary mutagenicity levels was also evaluated. Results: A non-significant increase of +1605 revertants/g creatinine in urinary mutagenicity during the workweek relative to levels observed on Sunday was observed for the total population. Subsequent multivariate regression analyses, with the subjects' weekday urinary mutagenicity levels as the dependent variable, revealed associations with environmental and mainstream tobacco smoke exposure, with the level of mutagenic contamination on surfaces with which the subjects had likely contact, with the subjects' inhalable particulate exposure level, with observed mild skin aberrations, and when the subjects had a slow acetylation phenotype. Similar associations, although weaker were observed with Sunday urinary mutagenicity levels as well, except for the association with slow acetylation phenotype. Based on measured exposure levels it could be estimated that a high potential for exposure to surface contamination with mutagenic activity increased weekday urinary mutagenicity by about 62% when compared to low exposed workers, while high inhalable particulate exposure levels increased weekday urinary mutagenicity levels by about 21%. Subjects with mild skin aberrations had an additional, non-significant, increase in weekday urinary mutagenic activity compared to subjects without any skin aberrations. Discussion: Results suggest that the dermal exposure route may contribute more to the level of genotoxic compounds in urine of rubber workers than the inhalation route. Although the study was limited in size, the results warrant further investigation in the importance of and ways to effectively control the dermal exposure route in the rubber industry.

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A simple test for acetylator phenotype using caffeine.

Cited by 186 publications

References 16 publications

Accuracy of Various Human NAT2 SNP Genotyping Panels to Infer Rapid, Intermediate and Slow Acetylator Phenotypes

Accuracy of Various Human NAT2 SNP Genotyping Panels to Infer Rapid, Intermediate and Slow Acetylator Phenotypes

PharmGKB summary

Exposure related mutagens in urine of rubber workers associated with inhalable particulate and dermal exposure

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