N-acetyltransferase SNPs: emerging concepts serve as a paradigm for understanding complexities of personalized medicine

被引:7
作者
Hein, David W. [1 ]
机构
[1] Univ Louisville, Dept Pharmacol & Toxicol, James Graham Brown Canc Ctr, Ctr Environm Genom & Integrat Biol,Sch Med, Louisville, KY 40292 USA
关键词
acetylator polymorphism; N-acetyltransferase; 1; 2; personalized medicine; single nucleotide polymorphisms; SINGLE-NUCLEOTIDE POLYMORPHISMS; COLORECTAL-CANCER RISK; NAT2 SLOW ACETYLATION; HETEROCYCLIC AMINE CARCINOGENS; DRUG-INDUCED HEPATOTOXICITY; SPANISH BLADDER-CANCER; RECOMBINANT HUMAN NAT1; RED MEAT INTAKE; HUMAN N-ACETYLTRANSFERASE-2; FUNCTIONAL-CHARACTERIZATION;
D O I
10.1517/17425250902877698
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Arylamine N-acetyltransferase 1 and 2 exhibit single nucleotide polymorphisms in human populations that modify drug and carcinogen metabolism. This paper updates the identity, location and functional effects of these single nucleotide polymorphisms and then follows with emerging concepts for understanding why pharmacogenetic findings may not be replicated consistently. Using this paradigm as an example, laboratory-based mechanistic analyses can reveal complexities such that genetic polymorphisms become biologically and medically relevant when confounding factors are more fully understood and considered. As medical care moves to a more personalized approach, the implications of these confounding factors will be important in understanding the complexities of personalized medicine.
引用
收藏
页码:353 / 366
页数:14
相关论文
共 89 条
[1]
Polymorphisms of human N-acetyltransferases and cancer risk [J].
Agundez, Jose A. G. .
CURRENT DRUG METABOLISM, 2008, 9 (06) :520-531
[2]
Unraveling ambiguous NAT2 genotyping data [J].
Agundez, Jose A. G. ;
Golka, Klaus ;
Martinez, Carmen ;
Selinski, Silvia ;
Blaszkewicz, Meinolf ;
Garcia-Martin, Elena .
CLINICAL CHEMISTRY, 2008, 54 (08) :1390-1394
[3]
BADAWI AF, 1995, CANCER RES, V55, P5230
[4]
BELL DA, 1995, CANCER RES, V55, P5226
[5]
Arylamine N-acetyltransferases:: What we learn from genes and genomes [J].
Boukouvala, S ;
Fakis, G .
DRUG METABOLISM REVIEWS, 2005, 37 (03) :511-564
[6]
Brockmoller J, 1996, CANCER RES, V56, P3915
[7]
Correlation between genotype and phenotype of the human arylamine N-acetyltransferase type 1 (NAT1) [J].
Bruhn, C ;
Brockmöller, J ;
Cascorbi, I ;
Roots, I ;
Borchert, HH .
BIOCHEMICAL PHARMACOLOGY, 1999, 58 (11) :1759-1764
[8]
Regulation of arylamine N-acetyltransferases [J].
Butcher, Neville J. ;
Tiang, Jacky ;
Minchin, Rodney F. .
CURRENT DRUG METABOLISM, 2008, 9 (06) :498-504
[9]
Proteasomal degradation of N-acetyltransferase 1 is prevented by acetylation of the active site cysteine -: A mechanism for the slow acetylator phenotype and substrate-dependent down-regulation [J].
Butcher, NJ ;
Arulpragasam, A ;
Minchin, RF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (21) :22131-22137
[10]
NAT2 slow acetylation and bladder cancer in workers exposed to benzidine [J].
Carreón, T ;
Ruder, AM ;
Schulte, PA ;
Hayes, RB ;
Rothman, N ;
Waters, M ;
Grant, DJ ;
Boissy, R ;
Bells, DA ;
Kadlubar, FF ;
Hemstreet, GP ;
Yin, S ;
Lemasters, GK .
INTERNATIONAL JOURNAL OF CANCER, 2006, 118 (01) :161-168