Concordance between the deduced acetylation status generated by high-speed Real-time PCR based NAT2 genotyping of seven single nucleotide polymorphisms and human NAT2 phenotypes determined by a caffeine assay

Rihs, Hans‐Peter; John, Andrea; Scherenberg, Michael; Seidel, Albrecht; Brüning, Thomas

doi:10.1016/j.cca.2006.08.010

Cited by 20 publications

(19 citation statements)

References 11 publications

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“…The inference of acetylation phenotype from NAT2 genotype is widely accepted, and the phenotype prediction accuracy can reach up to 100% [46]. However, lack of complete genotype-phenotype concordance is not uncommon [13–19].…”

Section: Discussionmentioning

confidence: 99%

N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians

Aklillu

Carrillo

Makonnen

et al. 2018

Eur J Clin Pharmacol

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Background and objectivesN-acetyltransferase 2 (NAT2) metabolize several drugs including isoniazid. We investigated the effect of genotype, geographical difference, and smoking habit on NAT2 phenotype in Ethiopians.MethodsGenotyping for NAT2 191G > A, 341 T > C, 590G > A, and 857G > A was performed in 163 unrelated healthy Ethiopians (85 living in Ethiopia and 78 living in Sweden). The NAT2 phenotype was determined using caffeine as a probe and log AFMU/(AFMU + 1X + 1 U) urinary metabolic ratio (MR) as an index.ResultsThe frequencies of NAT2*4, *5, *6, *7, and *14 haplotypes were 14.1, 48.5, 30.1, 5.5, and 1.8%, respectively. The frequencies of rapid (NAT2*4/*4), intermediate (heterozygous *4), and slow (no *4 allele) acetylator genotypes were 1.8, 24.6, and 73.6%, respectively. The distribution NAT2 MR was bimodal with 70% being phenotypically slow acetylators. NAT2 genotype (p < 0.0001) and country of residence (p = 0.004) independently predicted NAT2 phenotype. Controlling for the effect of genotype, ethnic Ethiopians living in Ethiopia had significantly higher NAT2 MR than those living in Sweden (p = 0.006). NAT2 genotype-phenotype concordance rate was 75%. Distinct country-of-residence-based genotype-phenotype discordance was observed. The proportion of phenotypically determined rapid acetylators was significantly higher and slow acetylators was lower in Ethiopians living in Ethiopia (39% rapid, 61% slow) than in Sweden (20% rapid, 80% slow). Sex and smoking had no significant effect on NAT2 MR.ConclusionsWe report a high prevalence of NAT 2 slow acetylators in Ethiopians and a conditional NAT2 genotype-phenotype discordance implicating a partial phenotype conversion and metabolic adaptation. Gene-environment interactions regulate NAT2 phenotype.

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Section: Discussionmentioning

confidence: 99%

N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians

Aklillu

Carrillo

Makonnen

et al. 2018

Eur J Clin Pharmacol

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“…Even though most studies showed a high concordance between genotypes and phenotypes, none of them showed 100% concordance. NAT2*4, NAT2*12A and NAT2*13 are related to rapid acetylator phenotypes, whereas NAT2*5, NAT2*6 and NAT2*7 are related to slow acetylator phenotypes (Butcher et al 2002;Cascorbi et al 1995;Hickman and Sim 1991;Rihs et al 2007;Woolhouse et al 1997). The highest discordance (86%) between genotypes and phenotypes was reported in the Hmong population (Southeast Asian immigrants from Laos since 1975) in Minnesota (Straka et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of promoter and coding regions of the arylamine N-acetyltransferase 2 (NAT2) gene in the Indonesian population: proposal for a new nomenclature

et al. 2007

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Polymorphisms of arylamine N-acetyltransferase 2 (NAT2) are reportedly associated with the risk of drug toxicities and development of various diseases. The present study examined NAT2 polymorphisms in both promoter and coding regions in the Indonesian population using PCR direct sequencing. The promoter and coding regions of NAT2 displayed 23 polymorphisms/variations, including eight new ones. Seven haplotypes in the promoter region and six haplotypes in the coding region were inferred. The haplotypes in promoter and coding regions showed limited combinations, and 13 combined haplotypes were inferred. The most frequent haplotypes were U1 (38.9%), U2 (33.5%) in the promoter region and NAT2*4 (37.3%), NAT2*6A (36.8%) in the coding region. When converted to predicted phenotypes, the studied population comprised 65.4% rapid acetylators and 35.6% slow acetylators according to bimodal distribution. According to trimodal distribution, frequencies of predicted phenotypes were 13.6, 50.8 and 35.6% for rapid, intermediate and slow acetylators, respectively. Frequencies of NAT2 alleles for the Indonesian population resembled those of other Southeast Asian populations. We also propose a new NAT2

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“…8,11 Additionally, the phenotype analysis, usually accommodated only bimodal distribution (slow and rapid group) 12,13 and does not differentiate between the intermediate group from the rapid group. Therefore, in the present study we conducted a study to define the rapid and intermediate NAT2 phenotype based on both genotyping and urinary assay and determine the concordance rate between both methods.…”

Section: 10mentioning

confidence: 99%

Differentiation of N-acetyltransferase 2 (NAT2) rapid and intermediate acetylator based on genotype and urinary assay

Yuliwulandari¹,

Prayuni²,

Usman³

et al. 2017

AMJ

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Concordance between the deduced acetylation status generated by high-speed Real-time PCR based NAT2 genotyping of seven single nucleotide polymorphisms and human NAT2 phenotypes determined by a caffeine assay

Cited by 20 publications

References 11 publications

N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians

N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians

Polymorphisms of promoter and coding regions of the arylamine N-acetyltransferase 2 (NAT2) gene in the Indonesian population: proposal for a new nomenclature

Differentiation of N-acetyltransferase 2 (NAT2) rapid and intermediate acetylator based on genotype and urinary assay

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