Acetylator status and N-acetyltransferase 2 gene polymorphisms; phenotype–genotype correlation with the sulfamethazine test

Taja‐Chayeb, Lucía; González-Fierro, Aurora; Miguez-Muñoz, C.; Trejo-Becerril, Catalina; Cruz-Hernández, Erick de la; Cantú, David; Agúndez, José A.G.; Vidal-Millán, Silvia; Gutiérrez, Olga; Dueñas‐González, Alfonso

doi:10.1097/fpc.0b013e32834bec2b

Cited by 13 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of slow acetylation activity SNPs has been linked to the risk of developing type 2 diabetes [7, 8]. The sample of healthy volunteers participating on this study showed a high prevalence of a slow acetylation phenotype consistent with previous reports with larger samples of Mexican [34, 37] and Central American populations [43]. This can be attributed to the admixture effect present on American mestizo groups [44, 45].…”

Section: Discussionsupporting

confidence: 86%

Expression and genotype-dependent catalytic activity of N-acetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1

Salazar‐González

Turiján-Espinoza

Hein

et al. 2018

Biochemical Pharmacology

View full text Add to dashboard Cite

N-acetyltransferase 2 (NAT2) catalyzes the biotransformation of numerous arylamine and hydrazine drugs and carcinogens. Genetic polymorphisms of NAT2 modify drug efficacy and toxicity and susceptibility to diseases such as cancer and type 2 diabetes. Expression of NAT2 has been documented in the liver and gastrointestinal tract but not in other tissues. Deacetylation of cytosolic proteins by sirtuins is a post-translational modification important in regulatory networks of diverse cellular processes. The aim of the present study was to investigate NAT2 expression in peripheral blood mononuclear cells (PBMC) and the effects of NAT2 genotype and Sirtuin 1 (SIRT1). Both NAT2 and SIRT1 proteins were expressed on PBMC. Their expression was more prevalent on CD3+ compared to CD19+ and CD56+ cell populations. N-acetylation capacity of PBMC exhibited a NAT2 gene-dose response toward the N-acetylation of isoniazid. Subjects with rapid NAT2 genotype showed an apparent V of 42.1 ± 2.4; intermediate NAT2 genotypes an apparent V of 22.6 ± 2.2; and slow acetylator NAT2 genotypes an apparent V of 19.9 ± 1.7 nM acetyl-isoniazid/24 h/million cells. The N-acetylation capacity of NAT2 in the presence of SIRT1 enhancer was significantly decreased (p < 0.001), conversely, the transient silencing of SIRT1 resulted in an increase of N-acetylation capacity (p < 0.001). These findings are the first report of NAT2 genotype-dependent expression on PBMC and post-translational modification by SIRT1. These findings constitute a substantial advance in our understanding of human N-acetyltransferase expression and a new much less invasive method for measurement of human NAT2 expression and phenotype.

show abstract

Section: Discussionsupporting

confidence: 86%

Expression and genotype-dependent catalytic activity of N-acetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1

Salazar‐González

Turiján-Espinoza

Hein

et al. 2018

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…As is apparent in Fig. , the coefficient of variation of the reported NAT2 activity is smaller in the fast than in the slow acetylator group due to a higher number of outliers, reducing the correlation between the genotype deduced phenotype and the actual enzyme activity in this group (based on previously reported data) . At least in this case, selection of genotypes with reduced activity profiles as proposed by González‐Vacarezza et al .…”

Section: Discussionmentioning

confidence: 79%

“…A 4‐SNP genotyping method has been proposed including the SNPs rs1801280, rs1799930, rs1799931 and rs1801279. However, due to the fact that in the Mexican population, the minor allele frequency of rs1801279 is below 0·05, volunteers were not tested for this allele . Accuracy of classification is expected to only increase marginally for the slow and fast acetylator genotypes by expanding from the 3‐SNP scheme to the 7‐SNP scheme.…”

Section: Discussionmentioning

confidence: 99%

“…Variability of NAT 2 Activity. If our 3‐ SNP typing algorithm (see section) were applied to the 122 M exican M estizos with reported genotypes and NAT 2 activities, it would result in 17, 57 and 48 individuals classified as having fast, intermediate and slow genotypes, respectively . Activities ( RU : relative units) within these groups would have coefficients of variation corresponding to 20·4%, 30·7% and 48·1%.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic selection of volunteers and concomitant dose adjustment leads to comparable hydralazine/valproate exposure

et al. 2014

View full text Add to dashboard Cite

show abstract

“…NAT2 *12A, NAT2 *12C, NAT2 *13 and NAT2 *18 have also been classified as rapid alleles. The remaining alleles are considered to be slow alleles (9–11). …”

Section: Introductionmentioning

confidence: 99%

Association of NAT2 polymorphisms with risk of colorectal adenomas: Evidence from 3,197 cases and 4,681 controls

Zhang

Qiu

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Previous studies have implicated NAT2 polymorphisms as risk factors for various types of cancer. Colorectal adenomas are recognized as a pre-neoplastic lesion. A growing body of research documenting the association of NAT2 polymorphisms with the risk of colorectal adenomas has yielded conflicting results. The aim of the present study was to derive a more precise estimation of this association. Meta-analyses assessing the association of NAT2 variants with colorectal adenomas were conducted and subgroup analyses on smoking status and the source of the controls were also performed. Eligible studies were identified for the period before March 2012. A total of seven case-control studies, including 3,197 cases and 4,681 controls, were selected following extensive searching and screening. In the overall data, no associations between NAT2 polymorphisms and colorectal adenomas were observed [odds ratio (OR), 1.04; 95% confidence interval (CI), 0.90–1.21]. However, in the subgroup analysis concerning smoking status, slow acetylator variants were revealed to be correlated with increased colorectal adenoma risk in individuals who have smoked (OR, 1.31; 95% CI, 1.04–1.64). In conclusion, the data of the present study suggested that NAT2 polymorphisms may be a risk factor for colorectal adenomas in individuals who have a history of smoking.

show abstract

Acetylator status and N-acetyltransferase 2 gene polymorphisms; phenotype–genotype correlation with the sulfamethazine test

Cited by 13 publications

References 32 publications

Expression and genotype-dependent catalytic activity of N-acetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1

Expression and genotype-dependent catalytic activity of N-acetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1

Genetic selection of volunteers and concomitant dose adjustment leads to comparable hydralazine/valproate exposure

Association of NAT2 polymorphisms with risk of colorectal adenomas: Evidence from 3,197 cases and 4,681 controls

Contact Info

Product

Resources

About