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

Background and objectives N-acetyltransferase 2 (NAT2) metabolize several drugs including isoniazid. We investigated the effect of genotype, geographical difference, and smoking habit on NAT2 phenotype in Ethiopians. Methods Genotyping for NAT2 191G > A, 341 T > C, 590G > A, and 857G > A...

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Bibliographic Details
Published in:European journal of clinical pharmacology 2018-07, Vol.74 (7), p.903-911
Main Authors: Aklillu, Eleni, Carrillo, Juan Antonio, Makonnen, Eyasu, Bertilsson, Leif, Djordjevic, Natasa
Format: Article
Language:English
Subjects:
Acetyltransferase
Biomedical and Life Sciences
Biomedicine
Discordance
Genotype & phenotype
Genotypes
Genotyping
Haplotypes
Health behavior
Health risk assessment
Isoniazid
Metabolism
N-Acetyltransferase 2
Pharmacogenetics
Pharmacology/Toxicology
Phenotypes
Population genetics
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Summary:Background and objectives N-acetyltransferase 2 (NAT2) metabolize several drugs including isoniazid. We investigated the effect of genotype, geographical difference, and smoking habit on NAT2 phenotype in Ethiopians. Methods Genotyping 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. Results The 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  
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-018-2448-y