[Identification of functionally significant mutations in NAT2 gene using biological microchips].
The product of gene NAT2 (N-acetyltransferase 2) is involved in the biotransformation system and participates in detoxication of some arylamine derivatives (in particular 2-aminofluorene, 4-aminobiphenyl and 4-naphthylamine) which are strongly mutagenic and carcinogenic. It also renders toxicological and pharmacological influence on a metabolism of medical products metabolized by the enzyme. We developed a microchip for detection of 16 functionally significant mutations coding 36 alleles of gene NAT2. Combinations of these alleles allow us to reveal more than 660 genotypes, which can be divided into four groups according acetylation phenotype: "fast" (R/R), "intermediate" (R/S), "slow" (S/S) and group with average or slow acetylating (R/S or S/S) alleles. The groups "R/S or S/S" include alleles, formed by a combination of 7 mutations (191G/A, 282C/T, 341T/C, 481C/T, 590G/A, 803A/G, 857G/A), theirs cis-trans position can be revealed by restriction analysis. In 37 of 71 DNA samples we unequivocally defined NAT2-genotypes, and other 34 samples have been characterized by more than two genotypes. 16 samples out of 34 had acetylation phenotype of group "R/S or S/S", which is characterized by the following combination of mutations: 282C/T, 341T/C, 481C/T, 590G/A and 803A/G. Thus, the developed biochip is a convenient screening method for primary detection of the majority of polymorphic replacements in gene NAT2.
Kozhekbaeva
Zh M
ZhM
Glotov
A S
AS
Gra
O A
OA
Goldenkova-Pavlova
I V
IV
Bruskin
S A
SA
Agafonova
E E
EE
Markarova
E V
EV
Abdeev
R M
RM
Korsunskaia
I M
IM
Piruzian
An L
AL
Barskiĭ
V E
VE
Zasedatelev
A S
AS
Nasedkin
T V
TV
D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D005787:Gene Frequency; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D017354:Point Mutation; D011110:Polymorphism, Genetic
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human