Accuracy of NAT2 SNP Genotyping Panels to Infer Acetylator Phenotypes in African, Asian, Amerindian and Admixed Populations

Abstract

A letter in response to: Hein DW, Doll MA. Accuracy of various human NAT2 SNP genotyping panels to infer rapid, intermediate and slow acetylator phenotypes.

Dietary Heterocyclic Amine Intake, NAT2 Genetic Polymorphism, and Colorectal Adenoma Risk: The Colorectal Adenoma Study in Tokyo

“…Furthermore, the NAT2 rapid and slow acetylation genotypes were inferred by genotyping only 3 SNPs, which might have caused some rapid acetylators to be misclassified as slow. Nevertheless these 3 SNPs were shown to infer acetylation phenotypes with 100% accuracy among a Japanese population (48), and any such misclassification is likely to be small. In summary, we found a significant positive association between higher MeIQ intake and colorectal adenoma risk in women but not in men.…”

Scientific Challenges and Implementation Barriers to Translation of Pharmacogenomics in Clinical Practice

“…Regardless of the choice of approach to identify the genotype-phenotype association, population variations in prevalence and relative importance of different allele variants, for example, CYP2D6, HLA-B, UGT1A1, and SLC6A4, remind investigators of the importance of ethnicity and population stratification [35,36], which could magnify the sample size 4 ISRN Pharmacology requirement for statistical power in most pharmacogenomic studies. For example, although the algorithms based on the work of Gage et al [37] and the International Warfarin Pharmacogenetics Consortium (IWPC) [38,39] are clinically useful, they do not include detection of the CYP2C9 * 8, an allele commonly occurring in African Americans.…”

A Four-SNP NAT2 Genotyping Panel Recommended to Infer Human Acetylator Phenotype

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A four-SNP NAT2 genotyping panel recommended to infer human acetylator phenotype We thank Suarez-Kurtz and colleagues for their Letter to the Editor [1] providing confirmation and expansion of the conclusions outlined in our paper recently published in Pharmacogenomics [2]. As described in our paper, we assessed the accuracy of NAT2 SNP genotyping panels to confer acetylator phenotype in cryopreserved human hepatocytes derived from a convenience sample of individuals in the USA with ethnic frequency similar to the 2010 US population census [2].

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“…As described in our paper, we assessed the accuracy of NAT2 SNP genotyping panels to confer acetylator phenotype in cryopreserved human hepatocytes derived from a convenience sample of individuals in the USA with ethnic frequency similar to the 2010 US population census [2]. A major strength of our published study [2] is the experimental measurement of acetylator phenotype whereas a major strength of the Suarez-Kurtz et al study [1] is an increased ethnic diversity of the sample set, including high percentages of African, Asian, Amerindian and admixed populations.Although our study [2] measured acetylator phenotype experimentally and the Suarez-Kurtz et al study [1] inferred acetylator phenotype, nevertheless the results and conclusions of the two studies are complementary. The overall conclusion from our published paper was that a NAT2 4-SNP genotype panel consisting of rs1801279 (191G>A), rs1801280 (341T>C), rs1799930 (590G>A) and rs1799931 (857G>A) infers NAT2 acetylator phenotype with high (experimentally determined as 98.4%) accuracy, and is recommended over the tagSNP, 2-SNP, 3-SNP (and, for economy of scale, the 7-SNP) genotyping panels, particularly in populations of non-European ancestry [2].…”