title: Clarifying haplotype ambiguity of NAT2 in multi-national cohorts.
abstract: 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.
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany. selinski@ifado.de
authors.forename: Silvia
authors.initials: S
authors.lastname: Selinski
authors.forename: Meinolf
authors.initials: M
authors.lastname: Blaszkewicz
authors.forename: Jose A G
authors.initials: JA
authors.lastname: Agundez
authors.forename: Carmen
authors.initials: C
authors.lastname: Martinez
authors.forename: Elena
authors.initials: E
authors.lastname: Garcia-Martin
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.forename: Klaus
authors.initials: K
authors.lastname: Golka
mesh_terms: D000107:Acetylation; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D005060:Europe; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human