IMR Press / FBS / Volume 5 / Issue 2 / DOI: 10.2741/S399

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Clarifying haplotype ambiguity of NAT2 in multi-national cohorts
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1 Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany
2 Department of Pharmacology, University of Extremadura, Badajoz, Spain
3 Department of Biochemistry and Molecular Biology, University of Extremadura, Badajoz, Spain

*Author to whom correspondence should be addressed.

Academic Editor: King-Thom Chung

Front. Biosci. (Schol Ed) 2013, 5(2), 672–684;
Published: 1 January 2013
(This article belongs to the Special Issue Arylamine induced carcinogenesis)

N-Acetyltransferase 2 (NAT2) is the key enzyme in aromatic amine metabolism. NAT2 genotyping requires a subsequent determination of the haplotype pairs (formerly: alleles) to derive the acetylation status. The chromosomal phase of the single nucleotide polymorphisms (SNPs) is unclear for about 2/3 of the genotypes. We investigated NAT2 genotypes of 1,234 bladder cancer cases and 2,207 controls from Germany, Hungary, Pakistan and Venezuela plus 696 further German cancer cases. We reconstructed NAT2 haplotypes using PHASE v2.1.1. We analysed if the variability of the NAT2 haplotypes affected the haplotype reconstruction. Furthermore, we compared population haplotype frequencies in three Caucasian control cohorts (German, Hungarian, Spanish), in Pakistanis and Venezuelans and the impact on bladder cancer. We conclude that a common haplotype reconstruction is feasible, enhances precision and reliability. Hungarian controls showed the largest intra-ethnic variability whereas the Pakistanis showed a haplotype distribution typical for Caucasians. The main differences could be observed for the slow haplotypes *5B, *6A and *7B. The association of slow NAT2 genotypes with bladder cancer risk was most prominent in the Venezuelan study group.

rs1801279 (G191A)
rs1041983 (C282T)
rs1801280 (T341C)
rs1799929 (C481T)
rs1799930 (G590A)
rs1208 (A803G)
rs1799931 (G857A)
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