title: Expression efficiency of NAT2 haplotypes in a Korean population.
abstract: Since NAT2 single-nucleotide polymorphisms (SNPs) are responsible for the efficacy of arylamines and hydrazine drugs, defining the effects of these SNPs in various ethnicities is an important factor in the development of personalized medicine. In the present study, we examined the expression efficiency of NAT2 using promoter haplotypes identified in a Korean population. To construct NAT2 promoter haplotypes, seven NAT2 promoter SNPs (rs4646241, rs4646242, rs4646243, rs4646267, rs4345600, rs4271002 and rs4646246) were genotyped in a total of 192 Korean subjects. A luciferase assay was performed using the three commonest haplotypes to evaluate enzyme expression level of NAT2 promoter haplotypes. The most common haplotype (TACGAGG) showed the lowest enzyme expression level (0.72 ± 0.06 relative light units (RLU)/[β-galactosidase]). The second (CGTAAGA) and third (TATAACA) commonest haplotypes showed intermediate and the highest enzyme expression level (0.99 ± 0.05 and 1.45 ± 0.11 RLU/[β-galactosidase]), respectively. Haplotype comparison among populations showed that Asian populations had a high proportion of the haplotype for lowest enzyme expression. Haplotype frequencies of Caucasian and African ethnicities were markedly different from those of Korean ethnicity. Results from the present study should contribute to the expansion of our current understanding of the pharmacogenetics field.
authors.affiliation: Clinical Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex.
authors.forename: Han Sung
authors.initials: HS
authors.lastname: Na
authors.forename: Jin Sol
authors.initials: JS
authors.lastname: Lee
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Shin
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Kang
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Myeon Woo
authors.initials: MW
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D056910:Republic of Korea
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human