+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Correlation between genotype and phenotype of the human arylamine N-acetyltransferase type 1 (NAT1)



Correlation between genotype and phenotype of the human arylamine N-acetyltransferase type 1 (NAT1)



Biochemical Pharmacology 58(11): 1759-1764



Arylamine N-acetyltransferase 1 (NAT1) conjugates several aromatic amines and their N-hydroxylated metabolites by N- or O-acetylation. NAT1 genotype and phenotype is known to be variable in human populations. In this study, we set out to measure the functional relevance of the frequent NAT1 gene variants for the activity in human red blood cells. Healthy German volunteers (N = 314) were genotyped for NAT1 alleles *3, *4, *10, *11, *14, and *15 using polymerase chain reactions and restriction fragment length pattern analysis, and NAT1 enzyme kinetic parameters were measured in a subset of 105 individuals using p-aminobenzoic acid as specific substrate. There was no functional difference between NAT1 alleles *4 and *10. In particular, there was no trend of increasing activity from NAT1*4/*4 to *4/*10 and *10/*10. Carriers of the NAT1 *11 and *14 alleles had a statistically significant lower enzyme activity compared with carriers of the *3, *4, or *10 alleles. Compared with the wild-type genotype NAT1*4/*4, activity of the NAT1*11/*11, NAT1*11/*10, and NAT1*11/*4 genotypes was reduced by 20.7%, 35.7%, and 31.5%, respectively. Activity of the NAT1*10/*14 and NAT1*4/*14 genotypes was reduced by 49.8% and 55.6%, respectively. The difference in NAT1 activity between the *4/*11 and *4/*14 genotypes was also significant (P < 0.01). The carrier of the NAT1*15/*15 genotype had no detectable enzyme activity. In conclusion, functional consequences of NAT1 mutations were tested in a large population. Activity in carriers of NAT1 alleles *3, *4, and *10 did not differ, alleles NAT1*11 and *14 appeared to be low activity alleles, and allele NAT1*15 had no activity.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010390087

Download citation: RISBibTeXText

PMID: 10571250

DOI: 10.1016/s0006-2952(99)00269-5


Related references

Placental expression of arylamine N-acetyltransferases: Evidence for linkage disequilibrium between NAT1*10 and NAT2*4 alleles of the two human arylamine N-acetyltransferase loci NAT1 and NAT2. Pharmacology & Toxicology 83(4): 149-157, 1998

Genotyping human arylamine N-acetyltransferase type 1 (NAT1): The identification of two novel allelic variants. Biochemical Pharmacology 55(3): 361-366, 1998

Arylamine N-acetyltransferase genotype in familial adenomatous polyposis Correlation with clinical phenotype. Gastroenterology 116(4 Part 2): A448, 1999

Phenotype of the most common "slow acetylator" arylamine N-acetyltransferase 1 genetic variant (NAT1*14B) is substrate-dependent. Drug Metabolism and Disposition: the Biological Fate of Chemicals 40(1): 198-204, 2012

Structure-function studies of human arylamine N-acetyltransferase NAT1 and NAT2: Functional analysis of recombinant NAT1/NAT2 chimeras expressed in escherichia coli. Journal of Biological Chemistry 269(43): 26830-26835, 1994

Functional analysis of arylamine N-acetyltransferase 1 (NAT1) NAT1*10 haplotypes in a complete NATb mRNA construct. Carcinogenesis 33(2): 348-355, 2012

Relation between genotype for human arylamine N-acetyltransferase and phenotype acetylation in the children under 2 years old. Therapie (Paris) 0(Suppl. ): 84, 1995

NATb/NAT1*4 promotes greater arylamine N-acetyltransferase 1 mediated DNA adducts and mutations than NATa/NAT1*4 following exposure to 4-aminobiphenyl. Molecular Carcinogenesis 51(8): 636-646, 2012

Differences between murine arylamine N-acetyltransferase type 1 and human arylamine N-acetyltransferase type 2 defined by substrate specificity and inhibitor binding. Bmc Pharmacology and Toxicology 15: 68, 2014

Expression of monomorphic arylamine N-acetyltransferase (NAT1) in human leukocytes. Journal of Pharmacology and Experimental Therapeutics 259(3): 1241-1246, 1991

Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow-acetylator allele common in African-Americans. Carcinogenesis 14(8): 1689-1692, 1993