臺灣不同族群間 N-乙醯轉移 2（NAT2）基因單一核X酸多型性的分布變異   全文下載

Variability in the Frequency of Single Nucleotide Polymorphisms of N-acetyl Transferase 2 (NAT2) Gene among the Different Ethnic Groups in Taiwan

先前研究的結果顯示，台灣不同原住民族群間，其人類白血球抗原的單一核?酸多型性（single nucleotide polymorphisms, SNPs）具有顯著差異，且單一族群內具有高度同質性。為瞭解台灣七個族群間藥品代謝酵素基因多型性之差異性，以Phase II 代謝之結合酵素N- 乙醯轉移?2（N-acetyl transferase 2, NAT2），進行單一核?酸多型性研究。本研究主要使用TaqMan 方法進行基因型分析，並以聚合?鏈鎖反應暨限制片段長度多型性（PCr-rFLP）方法，驗證NAT2 之三個單一核?酸多型性（NAT2*5、NAT2*6 及NAT2*7）。結果顯示在不同台灣族群中，NAT2 之3 個單一核?酸多型性的基因型分布有明顯的差異性（p < 0.05），其中緩慢乙醯化代謝之基因型分布率從客家人的32.0% 至排灣族的75.5%；於泰雅族中未發現NAT2*5 對偶基因，但排灣族中NAT2*5 對偶基因分布率則達31.6%；NAT2*6 及NAT2*7 單一核?酸多型性對偶基因在各族群中的分布率分別為11.2-37.0% 及17.0-53.0%。本研究結果顯示：台灣的原住民及漢人種族，在藥物代謝基因NAT2 之基因型上有明顯差異，可能導致不同人種在使用藥品時，導致產生不同的療效及不良藥品反應。未來，進一步研究台灣族群與其他相關藥品代謝酵素基因多型性的關係，以提供藥品治療時之資訊。"

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 (PCRRFLP). 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.