2011•Pharmacogenetics and GenomicsRequires access
Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 genotype
Silvia Selinski, Meinolf Blaszkewicz, Marie‐Louise Lehmann, Д Ю Овсянников, Oliver Moormann, Christoph Guballa, Alexander Kreß, Michael C. Tru, Holger Gerullis, T. Otto, Dimitri Barski, Günter Niegisch, Peter Albers, Sebastian Frees, Walburgis Brenner, Joachim W. Thüroff, Miriam Angeli-Greaves, Thilo Seidel, Gerhard Roth, H. Dietrich, Rainer Ebbinghaus, Hans M. Prager, Hermann M. Bolt, Michael Falkenstein, Anna Zimmermann, Torsten Klein, Thomas Reckwitz, H. Roemer, D. Löhlein, Wobbeke Weistenhöfer, Wolfgang Schöps, S.A.H. Rizvi, Muhammad Aslam, G. Bánfi, Imre Romics, Michael Steffens, Arif B. Ekici, Andreas Winterpacht, Katja Ickstadt, Holger Schwender, Jan G. Hengstler, Klaus Golka
Open publisher page 56 citations
Abstract
Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.