Relationship between NAT1 genotype and phenotype in a Japanese population.
NAT1, which biotransforms many carcinogens, is genetically polymorphic. This polymorphism has been postulated as a mechanism for susceptibility differences in cancer, possibly due to NAT1 activity differences. However, the relationship between NAT1 genotype and phenotype is not clear. In our study of 110 Japanese, the frequency of the NAT1*10 allele (0.53, 95% confidence interval 0.46-0.59) was higher than others have observed in Caucasians (0.16). From genotype frequency studies, 26.4% of the subjects belonged to the NAT1*10/*10 genotype, 53.6% to the NAT1*4/*10 genotype and 20% to the NAT1*4/*4 genotype. Neither NAT1*3 nor NAT1*11 genotype was seen in these subjects. In female subjects, we found higher NAT1 activity in NAT1*4/*10 subjects than in NAT1*4/*4 subjects (n = 49; 2.63 versus 2.16 nmol/min/mg protein). NAT1 activity-difference between NAT1*4/*10 and NAT1*10/*10 was not statistically significant. Thus, not only the presence of NAT1*10 allele, but also other factors are suspected of increasing NAT1 activities. After full sequencing of 10 subjects, five individuals having the highest activities and five individuals having the lowest activities, we found NAT1*18A and NAT1*18B to be in the high activity group and the low activity group, respectively. The genotypes containing these variants were heterozygous, i.e. NAT1*4/*18A and NAT1*4/*18B. Due to rare frequencies of these variants, they cannot be considered as other effective, genetic factors on NAT1 activity. Age and tobacco smoking did not affect the relationship between NAT1 genotype and phenotype.
Yang
M
M
Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, Arizona 72079, USA. myang@nctr.fda.gov
Katoh
T
T
Delongchamp
R
R
Ozawa
S
S
Kohshi
K
K
Kawamoto
T
T
D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism*; D044466:Asian People / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D007564:Japan; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology; D010641:Phenotype; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D012907:Smoking
D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; D010129:4-Aminobenzoic Acid