Variability in the Frequency of Single Nucleotide Polymorphisms of N-acetyl Transferase 2 (NAT2) Gene among the Different Ethnic Groups in Taiwan
FE-LIN LIN WU1,2,3, YUN-RU CHEN1, MARIE LIN4, HERNG-DER CHERN5 AND LI-JIUAN SHEN1,2,3*
1. School of Pharmacy, Medical College, National Taiwan University, Taipei, Taiwan (R.O.C.)
2. Graduate Institute of Clinical Pharmacy, Medical College, National Taiwan University, Taipei, Taiwan (R.O.C.)
3. Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan (R.O.C.)
4. Transfusion Medicine Laboratory, Mackay Memorial Hospital, Taipei, Taiwan (R.O.C.)
5. Center for Drug Evaluation, Taipei, Taiwan (R.O.C.)
(Received: November 26, 2007; Accepted: April 17, 2008)
ABSTRACT
Significant variations in the frequency of single nucleotide polymorphisms (SNPs) of human leukocyte antigen among Taiwan's aboriginal tribes and high homogeneity within each tribe have been reported. To identify variations in genetic polymorphisms of drug-metabolizing enzyme in seven of Taiwan's ethnic groups, the SNPs of N-acetyl transferase 2, a conjugation enzyme in phase II metabolism, were investigated. Methods: Three SNPs of NAT2, NAT2*5, NAT2*6, and NAT2*7, were determined by the TaqMan® method and subsequently confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results showed statistically significant variations in the frequency of NAT2 genotype categories according to the 3 SNPs of NAT2 within 7 Taiwanese ethnic groups (Chi-square = 32.08, p<0.05). The distribution of the frequency of the slow acetylator genotype ranged from 32.0% in the Hakka population to 75.5% in the Paiwan population. A lack of NAT2*5 SNP alleles was found in the Atayal population, while a NAT2*5 allele frequency of 31.6% was observed in the Paiwan group. The frequencies of allele NAT2*6 and NAT2*7 in the investigated ethnic groups ranged from 11.2-37.0% and 17.0-53%, respectively. Our results also showed the considerable variations in drug-metabolizing enzyme NAT2 genotypes among Taiwan's aboriginal and general population. The variation in the genetic polymorphisms of drug-metabolizing enzyme in Taiwan's groups is worthy of further study to understand different therapeutic and adverse drug responses in ethnic groups.
Key words: N-acetyltransferase 2, aboriginal, single nucleotide polylmorphism, Taiwan