Arylamine N-acetyltransferase (NAT2) genotypes in Africans (original) (raw)
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Pharmacogenetics …, 2003
This study was carried out to characterize the distribution of NAT2 allelic variants among a sample of three African populations. We determined the frequencies of major NAT2 allele clusters (NAT2 à 5, à 6, à 7 and à 14) using PCR/ restriction fragment length polymorphism and sequencing techniques. The genotypes predict slow acetylator phenotypes of 49, 38 and 52% among Tanzanians, Venda and Zimbabweans, respectively. The most common genotype was NAT2 à 4/ à 5. NAT2 à 5 was the most common allele while NAT2 à 7 was the least common. A new allele with two base changes occurring together, 481C>T and 590G>A, is reported. The frequency of the occurrence of the combination 481C>T and 590G>A, was found to be 9% (30/326), 7% (14/192) and 8% (18/234) among Zimbabweans, Venda and Tanzanians, respectively. The allele has been named NAT2 à 6E. Among Africans, the change 481C>T is not only associated with 341C>T (i.e. the NAT2 à 5 allele cluster) as in other populations, but also with 590G>A on the same allele. Pharmacogenetics
The study was carried out to investigate the distribution of arylamine N-acetyltransferase 2 (NAT2) allele frequencies associated with slow acetylation in healthy individuals from the three major Nigeria ethnic groups comprising of Hausa, Ibo and Yoruba. The single nucleotide polymorphisms (SNPs) in the NAT2 gene from three hundred unrelated subjects comprising, Hausa (N=98), Ibo (N=101) and Yoruba (N=101) who consented to the study were genotyped by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) techniques (481 C>T, 590 G>A) and DNA sequencing (191 G>A, 857 G>A). The allele frequencies of the investigated SNPs indicates that NAT2*4, wild-type (34%; 95% confidence interval (CI): 22-38%) is the most prevalent allele in Hausa, NAT2*6, G>A (29%; 95% CI: 22-37%) is the most common in Ibo while NAT2*5, 481 C>T (33%; 95% CI: 21-37%) is the most recorded in Yoruba populations. The most prevalent alleles in the three populations are the wild ...
Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 2007
Arylamine N-acetyltranferase 2 is the main enzyme responsible for the isoniazid metabolization into hepatotoxic intermediates and the degree of hepatotoxicity severity has been attributed to genetic variability in the NAT2 gene. The main goal of this study was to describe the genetic profile of the NAT2 gene in individuals from two different regions of Brazil: Rio de Janeiro and Goi´as States. Therefore, after preparation of DNA samples from 404 individuals, genotyping of the coding region of NAT2 was performed by direct PCR sequencing. Thirteen previously described SNPs were detected in these Brazilian populations, from which seven: 191 G>A; 282 C> T; 341 T >C; 481 C> T; 590 G>A; 803 A>G and 857 G>A are the most frequent in other populations. The presence of so-called ethnic-specific SNPs in our population is in accordance with the Brazilians’ multiple ancestry. Upon allele and genotype analysis, the most frequent NAT2 alleles were respectively NAT2*5B (33%), NAT2*6A (26%) and NAT2*4 (20%) being NAT2*5/*5 the more prevalent genotype (31.7%). These results clearly demonstrate the predominance in the studied Brazilian groups of NAT2 alleles associated with slow over the fast and intermediate acetylator genotypes. Additionally, in Rio de Janeiro, a significantly higher frequency of intermediate acetylation status was found when compared to Goi´as (42.5% versus 25%) (p = 0.05), demonstrating that different regions of a country with a population characterized by a multi-ethnic ancestry may present a large degree of variability in NAT2 allelic frequencies. This finding has implications in the determination of nationwide policies for use of appropriate anti-TB drugs.
Arylamine N-acetyltransferase 2 slow acetylator polymorphisms in unrelated Iranian individuals
European Journal of Clinical Pharmacology, 2004
Objective: To determine the frequency of mutations at the polymorphic gene coding for arylamine N-acetyltransferase 2 (NAT2, EC 2.3.1.5) and NAT2 genotypes associated with slow acetylation in healthy Iranian individuals. Methods: The polymorphisms in the NAT2 gene from 88 unrelated healthy subjects (48 men/40 women) from the general Tehran population were discriminated using polymerase chain reaction (PCR) with allele-specific primers (341 C>T) and PCR-restriction fragment length polymorphism analysis (481 C>T, 590 G>A, and 857 G>A). Results: Frequencies of the studied polymorphisms showed the most common alleles to be NAT2*4 (0.43) and NAT2*5, 481 C>T (0.32), followed by NAT2*6 (0.19) and NAT2*7 (0.06), previously referred to as WT, M1, M2, and M3, respectively. The most prevalent genotypes were NAT2*4/*5 [(31.8%; 95% confidence interval (CI): 29-34%] and *4/*4 (18.2%; 95% CI: 16-21%). When grouped according to the expected phenotypical effects, the resulting genotypes revealed the significant prevalence of the subjects with slow (32.9%) and intermediate (48.9%) acetylation status compared with wild-type rapid (18.2%) acetylators (P<0.01). Conclusions: The overall allele pattern and acetylator status distribution in Iranians displayed the considerable prevalence of ''slow acetylators'' over ''rapid acetylators,'' similar to those of Caucasians except for a minor difference observed in the frequency of the NAT2*7 allele. Nucleic acid testing for common NAT2 mutations might be a potentially useful tool for an accurate phe-notype interpretation and identification of Iranian individuals at risk.
American journal of human genetics, 1995
The polymorphic arylamine N-acetyltransferase (NAT2; EC 2.3.1.5) is supposed to be a susceptibility factor for several drug side effects and certain malignancies. A group of 844 unrelated German subjects was genotyped for their acetylation type, and 563 of them were also phenotyped. Seven mutations of the NAT2 gene were evaluated by allele-specific PCR (mutation 341C to T) and PCR-RFLP for mutations at nt positions 191, 282, 481, 590, 803, and 857. From the mutation pattern eight different alleles, including the wild type coding for rapid acetylation and seven alleles coding for slow phenotype, were determined. Four hundred ninety-seven subjects had a genotype of slow acetylation (58.9%; 95% confidence limits 55.5%-62.2%). Phenotypic acetylation capacity was expressed as the ratio of 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine after caffeine intake. Some 6.7% of the cases deviated in genotype and phenotype, but sequencing DNA of these probands revealed n...
Molecular analysis of the arylamine N-acetyltransferase polymorphism in a Spanish population
Clinical Pharmacology & Therapeutics, 1994
The arylamine N-acetyltransferase (NAT-2) polymorphism causes impaired drug metabolism in about half of the white population. By the combined use of polymerase chain reaction (PCR) and restriction mapping with the endonucleases Fok I and Dde I, we have studied the genetic basis underlying NAT-2 polymorphism in genotnic deoxyribonucleic acid from 245 healthy Spaniards. The study of three mutations at the NAT-2 gene locus by PCR analysis (namely, 481T, 590A, and 857A) revealed that all these mutations were present in Spaniards at similar frequencies as described in other white populations, strongly contrasting with genetic differences in the CYP2D6 polymorphism between Spaniards and other white subjects. The frequencies for NAT-2 mutations were different in Spaniards compared with Hispanics. About 12% of the subjects studied were incorrectly genotyped by the PCR test. Further studies involving restriction mapping of PCR products revealed the occurrence of at least five NAT-2 mutations that, alone or combined, were present in eight allelic variants of the NAT-2 gene. The allele frequencies were as follows: wild type, 25.
Arylamine N-acetyltransferase 2 genotypes in a Mexican population
Genetics and Molecular Research, 2012
NAT2 genotypes in Mexicans Turkish population was significantly different from ours. We conclude that the mixed-race Mexican population requires special attention because NAT2 genotype frequencies differ from those in other regions of the world.
Journal of Human Genetics, 2008
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
Pharmacogenomics, 2011
Functional variability at the arylamine N-acetyltransferase genes is associated with drug response in humans and may have been adaptive in the past owing to selection pressure from diet and exposure to toxins during human evolution. Aims-We have characterized nucleotide variation at the NAT1 and NAT2 genes, and at the NATP1 pseudogene in global human populations, including many previously under-represented African populations, in order to identify potential functional variants and to understand the role that natural selection has played in shaping variation at these loci in globally diverse populations.
Distribution of arylamine N-acetyltransferase 2 (nat2) genotypes among Omanis
Journal for scientific research. Medical sciences / Sultan Qaboos University, 2003
to determine the genotypes of arylamine N-acetyltransferase (NAT2) among 127 unrelated apparently healthy Omanis. Identify the most common known polymorphisms of NAT*2 gene namely, G(191)A, C(282)T, C(341)T, C(481)T, G(590)A, A(803)G and G(857)A using PCR-RFLP analysis. Eleven allele variants (3 alternative) and 30 different genotypes were determined. The commonest alleles were found to be NAT*5B, NAT2*6A and NAT*4 with corresponding frequencies of 0.362, 0.248 and 0.189 respectively. The overall frequency of rapid acetylator alleles was 0.25. A new allele variant containing G(590)A, C(282)T and T(341)C polymorphisms was found in one subject (was named NAT2*5J). The commonest genotypes were found to be 5B/5B, 5B/6A, 4/5B, 4/6A with frequencies 0.165, 0.157, 0.118, 0.110 and 0.079 respectively.