Single nucleotide polymorphism coverage and inference of N-acetyltransferase-2 acetylator phenotypes in wordwide population groups
| Autor: | Mateus Fuchshuber-Moraes, Claudio J. Struchiner, Guilherme Suarez-Kurtz, Esteban J. Parra |
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| Rok vydání: | 2016 |
| Předmět: |
Arylamine N-Acetyltransferase
Population Genome-wide association study Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Ethnicity Genetics Humans SNP General Pharmacology Toxicology and Pharmaceutics Allele 1000 Genomes Project education Molecular Biology Genetics (clinical) education.field_of_study Racial Groups Haplotype Acetylation Tag SNP Phenotype 030220 oncology & carcinogenesis Molecular Medicine Algorithms Genome-Wide Association Study |
| Zdroj: | Pharmacogenetics and Genomics. 26:363-369 |
| ISSN: | 1744-6872 |
| DOI: | 10.1097/fpc.0000000000000225 |
| Popis: | Objective Several algorithms have been proposed to reduce the genotyping effort and cost, while retaining the accuracy of N-acetyltransferase-2 (NAT2) phenotype prediction. Data from the 1000 Genomes (1KG) project and an admixed cohort of Black Brazilians were used to assess the accuracy of NAT2 phenotype prediction using algorithms based on paired single nucleotide polymorphisms (SNPs) (rs1041983 and rs1801280) or a tag SNP (rs1495741). Methods NAT2 haplotypes comprising SNPs rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208 and rs1799931 were assigned according to the arylamine N-acetyltransferases database. Contingency tables were used to visualize the agreement between the NAT2 acetylator phenotypes on the basis of these haplotypes versus phenotypes inferred by the prediction algorithms. Results The paired and tag SNP algorithms provided more than 96% agreement with the 7-SNP derived phenotypes in Europeans, East Asians, South Asians and Admixed Americans, but discordance of phenotype prediction occurred in 30.2 and 24.8% 1KG Africans and in 14.4 and 18.6% Black Brazilians, respectively. Paired SNP panel misclassification occurs in carriers of NATs haplotypes *13A (282T alone), *12B (282T and 803G), *6B (590A alone) and *14A (191A alone), whereas haplotype *14, defined by the 191A allele, is the major culprit of misclassification by the tag allele. Conclusion Both the paired SNP and the tag SNP algorithms may be used, with economy of scale, to infer NAT2 acetylator phenotypes, including the ultra-slow phenotype, in European, East Asian, South Asian and American populations represented in the 1KG cohort. Both algorithms, however, perform poorly in populations of predominant African descent, including admixed African-Americans, African Caribbeans and Black Brazilians. |
| Databáze: | OpenAIRE |
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