Relationship between NAT1 genotype and phenotype in a Japanese population

NAT1, which biotransforms many carcinogens, is genetically polymorphic. Thi s polymorphism has been postulated as a mechanism for susceptibility differ ences in cancer, possibly due to NAT1 activity differences. However, the re lationship between NAT1 genotype and phenotype is not clear. In our study o f 110 Japanese, the frequency of the NAT1*10 allele (0.53, 95% confidence i nterval 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 N AT1*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 subject s. 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 statis tically significant, Thus, not only the presence of NAT1*10 allele, but als o other factors are suspected of increasing NAT1 activities. After full seq uencing of 10 subjects, five individuals having the highest activities and five individuals having the lowest activities, we found NAT1*18A and NAT1*1 8B to be in the high activity group and the low activity group, respectivel y. 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 an d tobacco smoking did not affect the relationship between NAT1 genotype and phenotype. Pharmacogenetics 10:225-252 (C) 2000 Lippincott Williams & Wilk ins.