NAT2 gene polymorphisms in three indigenous groups in the Colombian Caribbean Coast region

Abstract

Objective: To study the NAT2 gene polymorphisms 481T, 590A and 857A in the Chimila, Wiwa and Wayuu indigenous groups of the Colombian Caribbean to determine the frequencies of the allelesNAT2*4, NAT2*5, NAT2*6, and NAT2*7 and to determine the types of acetylators present in these populations. Methods: A total of 202 subjects were studied: 47 Chimila, 55 Wiwa, and 100 Wayuu. The polymorphisms were idenjpgied using a real-time PCR method for allelic discrimination designed using Taqman of Applied Biosystems. Results: The following alleles were found at the highest frequency in the following groups: the NAT2*4 allele (wild type) in the Wayuu group (55.3%), the NAT2*5 allele in the Wiwa group (34.5%), and the NAT2*7 allele in the Chimila group (24.2%). A higher frequency of the rapid acetylator status was found in the Wayuu group (31.3%) and Chimila group (29.5%) compared with the Wiwa group (12.7%). The intermediate acetylator status distribution was very similar in all three groups, and the frequency of the slow acetylator status was higher in the Wiwa group (32.7%) compared with the Chimila and Wayuu groups (20.5% and 21.2%, respectively). Conclusion: The results demonstrated the allelic distribution and pharmacogenetic differences of the three groups studied and revealed the most frequent acetylator status and phenotype. Because of the high prevalence of slow acetylators, a greater incidence of tuberculosis (TB) drug-induced hepatotoxicity is predicted in these populations, with a higher frequency in the Wiwa group.

Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in <i>NAT2</i>gene, a Computational Analysis

“…Two other SNPs (rs1799929 and rs1208) were synonymous, showing tolerated (using SIFT) and benign (using PolyPhen-2) effects by computational analysis software (i.e. they do not alter the phenotype), and they have been identified as slow acetylator phenotype in a wet lab setting (these findings agree with another study) [10]. Another SNP (rs1799931 (G386E) was classified as slow-acetylator in wet lab and the produced protein was considered as slower acetylator in the aforementioned study [5,12,17].…”

“…Both genes are located on chromosome 8 and they have different functional roles. NAT2 is involved in phase II pathway of removal of toxic substances from the human body and metabolism of xenobiotics and arylamine by N-or O-acetylation [10]. The enzyme arylamine N-acetyltransferase type 2 (NAT2), encoded by the NAT2 gene, is a critical enzyme in clinical pharmacology [8].…”

“…It is located in chromosome 8, with an open reading frame of 870 bp and consists of 290 amino acids, with variable tissue expression levels and distribution [12,13]. The occurrence of the acetylator phenotype activity is divided into fast, intermediate, and slow phenotypes and was found to differ through the different ethnic groups [8,10,14,15]. Thus, low or no NAT2 -enzyme activity have been implicated as a leading cause of increased susceptibility to drug toxicity and many kinds of cancer [16,17].…”

Pharmacogenetic variability of tuberculosis biomarkers in native and mestizo Peruvian populations

“…12 Currently, it is recognized that genetic polymorphisms influence the metabolism of drugs used in the treatment of tuberculosis and are a risk factor for hepatotoxicity. 25 The relationship between an individual metabolization profile, based on SNPs of the NAT2 gene, and the efficacy or toxicity of isoniazid in the body has already been established. Ohno et al 26 demonstrated that people with a slow metabolizer profile are at increased risk of developing isoniazid-induced hepatotoxicity.…”

NAT2Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris

“…We also confirmed that the acetylator phenotypes are induced by these three SNPs at “ http://nat.mbg.duth.gr ”: rs1799929 is responsible for the rapid acetylator phenotype while rs1799930 and rs1799931 are responsible for the slow acetylator phenotype. We chose these SNPs, as they are among the most commonly used SNPs for inferring NAT2 acetylator phenotype [ 64 ], and rs 1799930 and rs 1799931 especially are defined to be the cause of 95% of the low enzymatic activity alleles [ 67 ].…”