美托洛尔,临床注释-2,变异和临床注释数据

美托洛尔

临床注释ID

1447681932

药物名称(英)

metoprolol

变异单倍型

CYP2D6*1, CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6, CYP2D6*9, CYP2D6*10, CYP2D6*17, CYP2D6*29, CYP2D6*31, CYP2D6*35, CYP2D6*41

基因

CYP2D6

证据级别

水平覆盖

水平修饰符

Tier 1 VIP

表现型类别(英)

Metabolism/PK

表现型类别

代谢/PK

分数

116.4375

PMID计数

计数的证据

表现型

高血压

表现型(英)

Hypertension

最新日期

2021/4/30 0:00:00

URL

https://www.pharmgkb.org/clinicalAnnotation/1447681932

专业人口(英)

专业人口

临床等位基因

id	等位基因	注释文本
1033	*41	The CYP2D641 allele has been assigned as a decreased function allele with an activity score of 0.5 by CPIC. Patients carrying the 41 allele in combination with a decreased or no function allele may have decreased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the *41 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1032	*35	The CYP2D635 allele is assigned as a normal function allele by CPIC. Patients carrying the 35 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased metabolism of metoprolol as compared to patients carrying two increased function alleles or an increased function allele in combination with a normal function allele. Patients carrying the *35 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased metabolism of metoprolol as compared to patients carrying an increased function allele with an activity value of 3 or greater in combination with a no function allele or a decreased function allele but increased metabolism of metoprolol as compared to patients with a no function allele in combination with a decreased or normal function allele or two decreased or no function alleles. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1031	*31	The CYP2D631 allele has been assigned as a no function allele by CPIC. Patients carrying the 31 allele in combination with a decreased, normal or no function allele may have decreased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 31 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 31 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1030	*29	The CYP2D629 allele has been assigned as a decreased function allele with an activity score of 0.5 by CPIC. Patients carrying the 29 allele in combination with a decreased or no function allele may have decreased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the *29 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1029	*17	The CYP2D617 allele has been assigned as a decreased function allele with an activity score of 0.5 by CPIC. Patients carrying the 17 allele in combination with a decreased or no function allele may have decreased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the *17 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1028	*10	The CYP2D610 allele has been assigned as a decreased function allele with an activity value of 0.25 by CPIC. Patients carrying the 10 allele in combination with a decreased or no function allele may have decreased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 10 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 10 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1027	*9	The CYP2D69 allele has been assigned as a decreased function allele with an activity score of 0.5 by CPIC. Patients carrying the 9 allele in combination with a decreased or no function allele may have decreased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the *9 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1026	*6	The CYP2D66 allele has been assigned as a no function allele by CPIC. Patients carrying the 6 allele in combination with a decreased, normal or no function allele may have decreased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 6 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 6 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1025	*5	The CYP2D65 allele has been assigned as a no function allele by CPIC. Patients carrying the 5 allele in combination with a decreased, normal or no function allele may have decreased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 5 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 5 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1024	*4	The CYP2D64 allele has been assigned as a no function allele by CPIC. Patients carrying the 4 allele in combination with a decreased, normal or no function allele may have decreased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 4 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 4 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1023	*3	The CYP2D63 allele has been assigned as a no function allele by CPIC. Patients carrying the 3 allele in combination with a decreased, normal or no function allele may have decreased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 3 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 3 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of metoprolol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1022	*2	The CYP2D62 allele is assigned as a normal function allele by CPIC. Patients carrying the 2 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased metabolism of metoprolol as compared to patients carrying two increased function alleles or an increased function allele in combination with a normal function allele. Patients carrying the *2 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased metabolism of metoprolol as compared to patients carrying an increased function allele with an activity value of 3 or greater in combination with a no function allele or a decreased function allele but increased metabolism of metoprolol as compared to patients with a no function allele in combination with a decreased or normal function allele or two decreased or no function alleles. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.
1021	*1	The CYP2D61 allele is assigned as a normal function allele by CPIC. Patients carrying the 1 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased metabolism of metoprolol as compared to patients carrying two increased function alleles or an increased function allele in combination with a normal function allele. Patients carrying the *1 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased metabolism of metoprolol as compared to patients carrying an increased function allele with an activity value of 3 or greater in combination with a no function allele or a decreased function allele but increased metabolism of metoprolol as compared to patients with a no function allele in combination with a decreased or normal function allele or two decreased or no function alleles. This annotation only covers the pharmacokinetic relationship between CYP2D6 and metoprolol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metoprolol metabolism.

临床证据

id	证据的ID	总结
4812	1043859096	CYP2D6 9 + 29 + 45 + 46 + 17 + 10 is associated with decreased metabolism of metoprolol in people with Hypertension as compared to CYP2D6 *1.
4811	1043859051	CYP2D6 4 + 3 + 5 + 6 is associated with decreased metabolism of metoprolol in people with Hypertension as compared to CYP2D6 *1.
4810	1184986272	CYP2D6 35 is not associated with increased enzyme activity of CYP2D6 when assayed with debrisoquine, dextromethorphan or metoprolol in yeast cells as compared to CYP2D6 1.
4809	1184756941	CYP2D6 29/29 is associated with decreased metabolism of dextromethorphan or metoprolol in healthy individuals as compared to CYP2D6 1/1 + 1/2.
4808	1184756913	CYP2D6 5/17 is associated with decreased metabolism of codeine, debrisoquine, dextromethorphan or metoprolol in healthy individuals as compared to CYP2D6 17/17 + 1/1.
4807	1184756902	CYP2D6 17/17 is associated with decreased metabolism of debrisoquine, dextromethorphan or metoprolol in healthy individuals as compared to CYP2D6 1/1 + 1/2.
4806	1184756692	CYP2D6 *31 is associated with decreased enzyme activity of CYP2D6 when assayed with debrisoquine, dextromethorphan or metoprolol in yeast cells.
4805	1184756685	CYP2D6 4/31 (assigned as poor metabolizers phenotype) is associated with decreased metabolism of metoprolol in healthy individuals.
4804	1184756327	CYP2D6 4/20 (assigned as poor metabolizers phenotype) is associated with decreased enzyme activity of CYP2D6 when assayed with metoprolol.
4803	1184000492	CYP2D6 1/4 + 4/4 are associated with increased plasma metoprolol concentrations when treated with metoprolol as compared to CYP2D6 1/1.
4802	1043859395	CYP2D6 10 is associated with decreased metabolism of metoprolol in healthy individuals as compared to CYP2D6 1.
4801	1043859140	CYP2D6 2 is not associated with decreased metabolism of metoprolol in people with Hypertension as compared to CYP2D6 1.
4800	1043859002	CYP2D6 2 is not associated with decreased clearance of metoprolol as compared to CYP2D6 1.
4799	1043858995	CYP2D6 10 is associated with decreased clearance of metoprolol as compared to CYP2D6 1.
4798	1450944140	Allele A is associated with increased concentrations of metoprolol in healthy individuals as compared to allele G.
4797	751923645	Genotype del/del is associated with increased plasma concentrations of metoprolol when treated with metoprolol.
4796	769181593	Allele T is associated with increased plasma concentrations of metoprolol and greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in non-PMs. when treated with metoprolol as compared to allele C.
4795	1450944125	Allele A is not associated with increased concentrations of metoprolol in healthy individuals as compared to allele G.
4794	1447676621	CYP2D6 normal metabolizers are associated with increased clearance of metoprolol in women with Pregnancy as compared to CYP2D6 intermediate metabolizers.
4793	1183685331	CYP2D6 poor metabolizer is associated with increased peak plasma metoprolol concentration (CMax/dose), increased area under the concentration-time curve (AUC/dose), increased elimination half-life, and decreased apparent oral clearance (CL/F) when treated with metoprolol as compared to CYP2D6 ultra-metabolizer phenotype.
4792	PA166104995	Annotation of DPWG Guideline for metoprolol and CYP2D6

临床病史

id	类型	评论
797	Update	Added DPWG guideline as evidence. Moved 45 and 46 to a new CA as these alleles are not covered by the guideline. Rewrote phenotype descriptions to fit LOE 1A template.
796	Update	CA score added as part of scoring system release. LOE assigned following curator review.
795	Update	Minor edits to phenotype descriptions
794	Update	Added text to indicate where CPIC function is different from VA in this instance.
793	Update	Added annotation for *2.
792	Update	There were multiple VAs from same paper that needed to be combined into 3 VAs for PM, IM and EM, this dropped the score to 2A.
791	Update	Updated to new format.
790	Update	replaced nonfunctional with no and reduced with decreased function
789	Update	Added PMID 10471072, 15726636, 11823760, 11692084. Removed PMID 18784654, 24193112 (HR and blood pressure), 24637943, 2818117
788	Update
787	Create

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