Arylamine N-acetyltransferase 1 (NAT1) genotypes in a Lebanese population

Abstract

The frequency distributions of human N-acetyltransferase 1 (NAT1*) alleles in various ethnic groups are largely unknown. This lack of information is in contrast to the many studies of ethnic differences in NAT2* alleles and phenotypes. Increasing interest in NAT1 due to its potential roles in carcinogen metabolism and cancer risk makes it desirable to know the distribution of NAT1* alleles in various populations. Using a polymerase chain reaction-restriction fragment length polymorphism genotyping assay, the frequency of NAT1* alleles in a Lebanese population was determined. Of 84 NAT1* alleles assayed, 56% were NAT1*4. Alleles NAT1*3, *10, and *14 were found at frequencies of 0.036, 0.107, and 0.238, respectively. Five additional alleles (6%) differed from previously reported alleles. Nearly 50% of the population were heterozygous for a NAT1*14 allele. The unusually high frequency of NAT1*14 alleles in Lebanese may be useful for epidemiological studies of the effects of the NAT1 polymorphism in this population.

Pharmacogenetics of the arylamine N-acetyltransferases

“…[16][17][18]79,81,82 Interestingly, a much higher frequency of the NAT1*14 allele (25%) was reported for a Lebanese population. 83 Since no homozygous individuals were identified in the above study, 50% of the Lebanese population had a slow acetylator genotype. This indicates that NAT1, like NAT2, shows considerable interethnic variability.…”

Functional effects of single nucleotide polymorphisms in the coding region of human N-acetyltransferase 1

“…[6][7][8][9][10] The biological plausibility of these associations is based upon the role of human NAT1 in the metabolism of endogenous or exogenous agents. Single nucleotide polymorphisms (SNPs) in the human NAT1 coding region, present in less than 5% of Americans, Canadians and Europeans 11 but present in 25% of Lebanese 12 have been shown to modify risk of spina bifida. 10 Understanding the functional effects of SNPs in the NAT1 coding region is necessary to apply biological plausibility toward the associations observed with various diseases.…”

Urinary Bladder Cancer Risk Factors: A Lebanese Case-Control Study

“…Second, cases and controls showed distinct clustering patterns of NAT1 alleles. Knowing the high frequency of NAT1*14A in Lebanese based on a previous study we conducted in a Lebanese community residing in Detroit, Michigan, our study suggests NAT1*14A as a possible biomarker (Dhaini et al, 2000). Our study did not investigate schistosomiasis as a potential risk factor since this infection is very rare in Lebanon, and may be more relevant in countries like Egypt (Mostafa et al, 1999).…”

“…Of particular importance are the N-Acetyltransferase (NAT) enzymes, known to mediate metabolism of bladder carcinogens, mainly aromatic amines and heterocyclic amines. We have reported NAT1 to have an unusual allelic frequency distribution in a Lebanese community residing in Michigan in an earlier study (Dhaini et al, 2000).…”

“…The sample size for this study was guided by power analysis that revolved around the following: power of 80%; Type 1 error of 5%; and estimated OR of 3; and the proportion of exposure of suspected NAT1 alleles among the cases (21.4% based on data observed in an earlier study) (Butcher et al, 1998;Hughes et al, 1998;Dhaini et al, 2000). A ratio of 1:2 of cases to controls was made use of.…”