加利福尼亚州南部非裔美国人CYP2D6基因多态性与酶活性分析。
Analysis of the CYP2D6 gene polymorphism and enzyme activity in African-Americans in southern California.
作者信息
Wan Y J, Poland R E, Han G, Konishi T, Zheng Y P, Berman N, Lin K M
机构信息
Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, USA.
出版信息
Pharmacogenetics. 2001 Aug;11(6):489-99. doi: 10.1097/00008571-200108000-00004.
Despite its importance in drug metabolism and disease susceptibility, CYP2D6 activity and genetic polymorphism have rarely been investigated in African-American populations. In order to bridge this gap, we examined the genotype and phenotype of the enzyme in 154 African-American (AA) and 143 Caucasian (C) normal volunteers. AAs are significantly more likely to possess *17 and *5, but less likely to have *4. Overall, the two groups were similar in their CYP2D6 activity as measured with dextromethorphan as the probe (metabolic ratio 2.21 +/- 0.78 for AAs; 2.11 +/- 0.86 for Cs; t = 1.02, NS). Two of four AAs and six of seven Cs were classified as poor metabolizers and have two nonfunctioning alleles. CYP2D6 activity is determined by *17, *4, *5 and age in AAs (r2 = 0.33, f = 18.8, P < 0.001) and by *4 and *XN in Cs (r2 = 0.14, f = 10.8, P < 0.001). These results support previous findings demonstrating the importance of *17 in determining CYP2D6 activity in AAs.
尽管细胞色素P450 2D6（CYP2D6）在药物代谢和疾病易感性中具有重要作用，但其活性和基因多态性在非裔美国人中却鲜有研究。为了填补这一空白，我们检测了154名非裔美国（AA）正常志愿者和143名高加索（C）正常志愿者的该酶基因型和表型。非裔美国人携带17和5的可能性显著更高，但携带4的可能性更低。总体而言，以右美沙芬为探针检测时，两组的CYP2D6活性相似（非裔美国人的代谢率为2.21±0.78；高加索人为2.11±0.86；t = 1.02，无显著性差异）。四名非裔美国人中有两名、七名高加索人中有六名被归类为慢代谢者，且有两个无功能等位基因。非裔美国人的CYP2D6活性由17、4、5和年龄决定（r2 = 0.33，f = 18.8，P < 0.001），而高加索人的CYP2D6活性由4和XN决定（r2 = 0.14，f = 10.8，P < 0.001）。这些结果支持了先前的研究发现，即*17在决定非裔美国人CYP2D6活性方面具有重要作用。
Zotero 插件