Johansson I, Yue Q Y, Dahl M L, Heim M, Säwe J, Bertilsson L, Meyer U A, Sjöqvist F, Ingelman-Sundberg M
Department of Physiological Chemistry, Karolinska Institute, Stockholm, Sweden.
Eur J Clin Pharmacol. 1991;40(6):553-6. doi: 10.1007/BF00279968.
The Far Eastern and Caucasian populations are strikingly different with respect to the debrisoquine/sparteine hydroxylation polymorphism. The number of poor metabolizers, as defined for Caucasians, is very low among Chinese and Japanese. We investigated the molecular basis for this difference by analysis of the CYP2D6 gene in 115 Chinese subjects, combined with phenotypic classification of codeine and debrisoquine metabolism. A correlation between the rates of metabolism of these two drugs and genotype, as analyzed by RFLP using XbaI, was observed among the Chinese. A high frequency (37%) of alleles indicative of gene insertions (reflected by XbaI 44kb fragments) was recorded in the Chinese, but was not associated with the poor metabolizer phenotype, as it is in Caucasians. PCR amplification of part of the CYP2D6 gene with mutation specific primers for CYP2D6A (29A) and CYP2D6B (29B) allelic variants revealed that the XbaI 44kb fragment in Chinese apparently contains a functional CYP2D6 gene, in contrast to the situation among Caucasians. The results provide a molecular explanation of the interethnic difference in the metabolism of drugs affected by the debrisoquine hydroxylation polymorphism.
在异喹胍/鹰爪豆碱羟基化多态性方面，远东人群和高加索人群存在显著差异。按照高加索人的定义，在中国人和日本人中，代谢缓慢者的数量非常少。我们通过分析115名中国受试者的CYP2D6基因，并结合可待因和异喹胍代谢的表型分类，研究了这种差异的分子基础。在中国人群中，观察到这两种药物的代谢速率与使用XbaI通过限制性片段长度多态性（RFLP）分析的基因型之间存在相关性。在中国人群中记录到高频率（37%）的指示基因插入的等位基因（由XbaI 44kb片段反映），但与高加索人不同，它与代谢缓慢者表型无关。用针对CYP2D6A（29A）和CYP2D6B（29B）等位基因变体的突变特异性引物对CYP2D6基因的部分进行PCR扩增，结果显示，与高加索人群的情况相反，中国人的XbaI 44kb片段显然包含一个功能性CYP2D6基因。这些结果为受异喹胍羟基化多态性影响的药物代谢的种族间差异提供了分子解释。
