id	等位基因	注释文本
555	*2xN	The CYP2D62xN alleles (2x2 and 2x鈮?) are assigned as increased function alleles by CPIC. Patients carrying a 2xN allele with an activity value of 3 or greater in combination with a normal, increased, decreased or no function allele may have an increased risk of toxicity when treated with tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a 2xN allele with an activity value of 2 in combination with an increased or normal function allele or a decreased function allele with an activity value of 0.5 may also have an increased risk of toxicity when treated with tramadol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying a 2xN allele with an activity value of 2 in combination with a no function allele or a decreased function allele with an activity value of 0.25 may have a similar risk of toxicity when treated with tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. Other genetic and clinical factors may also influence risk of tramadol toxicity.
554	*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 risk of toxicity when treated with tramadol as compared to patients carrying two increased function alleles or an increased function allele in combination with a normal function allele or a decreased function allele with an activity value of 0.5. Patients carrying the *2 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased risk of toxicity when treated with tramadol 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 with an activity value of 0.25 but a similar risk of toxicity when treated with tramadol 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. Other genetic and clinical factors may also influence risk of tramadol toxicity.
553	*1xN	The CYP2D61xN alleles (1x2 and 1x鈮?) are assigned as increased function alleles by CPIC. Patients carrying a 1xN allele with an activity value of 3 or greater in combination with a normal, increased, decreased or no function allele may have an increased risk of toxicity when treated with tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a 1xN allele with an activity value of 2 in combination with an increased or normal function allele or a decreased function allele with an activity value of 0.5 may also have an increased risk of toxicity when treated with tramadol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying a 1xN allele with an activity value of 2 in combination with a no function allele or a decreased function allele with an activity value of 0.25 may have a similar risk of toxicity when treated with tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. Other genetic and clinical factors may also influence risk of tramadol toxicity.
552	*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 risk of toxicity when treated with tramadol as compared to patients carrying two increased function alleles or an increased function allele in combination with a normal function allele or a decreased function allele with an activity value of 0.5. Patients carrying the *1 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased risk of toxicity when treated with tramadol 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 with an activity value of 0.25 but a similar risk of toxicity when treated with tramadol 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. Other genetic and clinical factors may also influence risk of tramadol toxicity.

id	证据的ID	总结
14540	1444694442	CYP2D6 2/2xN is associated with increased risk of Respiratory Insufficiency when treated with tramadol.
14539	1183618150	CYP2D6 1/1xN is associated with increased risk of severe cardiotoxicity (refractory cardiac arrest) when treated with tramadol as compared to CYP2D6 1/1.
14538	1183618106	CYP2D6 1xN is associated with Respiratory Insufficiency when treated with tramadol as compared to CYP2D6 1/*1.
14537	PA166104959	Annotation of DPWG Guideline for tramadol and CYP2D6
14439	PA166228101	Annotation of CPIC Guideline for tramadol and CYP2D6

id	类型	评论
18	Update	Added DPWG guideline as evidence
17	Update	CA score added as part of scoring system release. LOE assigned following curator review.
16	Update	Minor edits to phenotype descriptions
15	Update	Added PMID 21691803 to evidence and rewrote phenotype descriptions to be on toxicity more generally rather than discrete types of ADR. Added CPIC guideline.
14	Create	Created

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