Research progress on the factors of CYP2D6 genotyping

doi:10.3969/j.issn.1673-8640.2024.03.015

Abstract

Abstract:

Cytochrome P450 family 2 subfamily D member 6（CYP2D6）is one of most important drug metabolism enzymes in the cytochrome P450 family. It mainly metabolizes many drugs，including antidepressants，antipsychotics and opioids. The complexity of CYP2D6 gene locus and allelic variation can be translated into the polymorphism of CYP2D6. To date，over 170 allelic variations have been published. CYP2D6 activity is highly variably ranging from no activity to ultrarapid metabolism. The phenotypes are categorized into ultrarapid metabolizer，normal metabolizer，intermediate metabolizer and poor metabolizer. With the development of individualized medicine，the CYP2D6 genotyping can utilize the pharmacogenetics and genotyping as part of the clinical decision-making process. The complexity of CYP2D6 allelic variations includes single nucleotide polymorphism，insertion，deletion，gene copy number variation and gene rearrangement. The CYP2D6 gene not only had individualized differences，but also the frequency of alleles between different races was different. Furthermore，CYP2D6 had a non-functional gene CYP2D7 with high homology，so its phenotype prediction by CYP2D6 genotyping was a challenging task. This review summarizes the polymorphism of CYP2D6 gene and the complexity of CYP2D6 genotyping，and also summarizes the impact of different allelic variations on CYP2D6 genotyping. It is valuable for clinical laboratories to perform CYP2D6 genotyping for phenotype prediction in the future.

Key words: Cytochrome P450 family 2 subfamily D member 6, Genotyping, Variation, Allele, Gene polymorphism

CLC Number:

R446.7

SHEN Jinjin, XUE Han, LI Jinfu, GAO Lifei, ZHENG Yehuan. Research progress on the factors of CYP2D6 genotyping[J]. Laboratory Medicine, 2024, 39(3): 291-297.

Figures/Tables 1

References 53

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等位基因	活性评分/分	东亚人群频率/%	等位基因功能	基因突变
*1	1.0	25.78	正常
*1×2	2.0	0.34	提高	*1双拷贝基因
*2	1.0	11.92	正常	2851C>T，4181G>C
*2×2	2.0	0.46	提高	*2双拷贝基因
*2×≥3	≥3.0	0.10	提高	*2至少有三拷贝基因
*4	0.0	0.53	无	1847G>A
*5	0.0	4.82	无	CYP2D6整基因缺失
*9	0.25	0.17	减弱	2616delAAG
*10	0.25	42.84	减弱	100C>T，4181G>C
*10×2	0.5	0.59	减弱	*10双拷贝基因
*13	0.0	0.13	无	CYP2D7-CYP2D6 hybrid gene
*14	0.5	0.47	减弱	1759G>A，2851C>T，4181G>C
*18	0.0	0.13	无	4135-4136insTGCCCACTG
*21	0.0	0.35	无	2580-2581insC，2851C>T，4181G>C
*34	1.0	0.89	正常	2851C>T
*36	0.0	1.14	无	100C>T， 4129C>G，4132A>G，4156C>T+4157A>C，4159G>C，4165T>G，4168G>A+4169C>G，4181G>C
*36×2	0.0	0.41	无	*36双拷贝基因
*39	1.0	0.56	正常	4181G>C
*41	0.25	2.32	减弱	2851C>T，2989G>A，4181G>C
*49	0.5	0.99	减弱	100C>T，1612T>A，4181G>C
*52	0.25	0.16	减弱	100C>T，3878G>A，4181G>C
*60	0.0	0.14	无	1888-1889insTA
*65		2.95	功能不清	100C>T，2851C>T，4181G>C
*69	0.0	1.00	无	100C>T，2851C>T，2989G>A，4181G>C

等位基因	活性评分/分	东亚人群频率/%	等位基因功能	基因突变
*1	1.0	25.78	正常
*1×2	2.0	0.34	提高	*1双拷贝基因
*2	1.0	11.92	正常	2851C>T，4181G>C
*2×2	2.0	0.46	提高	*2双拷贝基因
*2×≥3	≥3.0	0.10	提高	*2至少有三拷贝基因
*4	0.0	0.53	无	1847G>A
*5	0.0	4.82	无	CYP2D6整基因缺失
*9	0.25	0.17	减弱	2616delAAG
*10	0.25	42.84	减弱	100C>T，4181G>C
*10×2	0.5	0.59	减弱	*10双拷贝基因
*13	0.0	0.13	无	CYP2D7-CYP2D6 hybrid gene
*14	0.5	0.47	减弱	1759G>A，2851C>T，4181G>C
*18	0.0	0.13	无	4135-4136insTGCCCACTG
*21	0.0	0.35	无	2580-2581insC，2851C>T，4181G>C
*34	1.0	0.89	正常	2851C>T
*36	0.0	1.14	无	100C>T， 4129C>G，4132A>G，4156C>T+4157A>C，4159G>C，4165T>G，4168G>A+4169C>G，4181G>C
*36×2	0.0	0.41	无	*36双拷贝基因
*39	1.0	0.56	正常	4181G>C
*41	0.25	2.32	减弱	2851C>T，2989G>A，4181G>C
*49	0.5	0.99	减弱	100C>T，1612T>A，4181G>C
*52	0.25	0.16	减弱	100C>T，3878G>A，4181G>C
*60	0.0	0.14	无	1888-1889insTA
*65		2.95	功能不清	100C>T，2851C>T，4181G>C
*69	0.0	1.00	无	100C>T，2851C>T，2989G>A，4181G>C