final Flashcards
(117 cards)
The individual above has 3 copies of the CYP2D6 gene, assuming that all 3 copies code for normal function enzymes, the CYP2D6 phenotype assignment would be an –
UM
– is one of the rare pharmacogenes where people can inherit more than
two copies of the gene
CYP2D6
(COPY NUMBER VARIATION)
Some individuals may carry just one copy of the CYP2D6 gene,
Commonly reported as –* allele, which means the allele is —
*5 allele
deleted
The function of CYP2D6 / 2D7 hybrids depends on the — variants present in the hybrid gene and is for the most part still under investigation
-CYP2D6
-this is called the Hybridization of the CYP2D6 gene with the CYP2D7 pseudogene, where parts of the CYP2D6 gene are often deleted.
-CYP2D6 / 2D7 hybrids can also be on the same chromosome strand with a normal copy of the CYP2D6 gene.
-It is important to know whether the genetic testing laboratories can identify CYP2D6 hybrids
1/2 duplication
means
Means the patient has a *2 variant and more than 2 copies of the CYP2D6 gene, but it is not known how many extra copies the patient has
1xN/2
Means the patient has more than 2 copies of the CYP2D6 gene, and that the *1 allele is duplicated, but it is unknown how many duplicated copies exist
(1/2)xN
Means the patient has three or more copies of the CYP2D6 gene but it is unknown which allele is duplicated and how many copies the patient actually has
what are the values of the activity score system used to assign CYP2D6 phenotypes (from UM to PM)
-UM >2.25
-NM 1.25<x<2.25
-IM 0 <x<1.25
-PM 0
what are the values of the activity value system used to assign CYP2D6 enzyme functional status
-Increased function: >1
-Normal function: 1
-Decreased function: 0.25 and 0.5
-No function: 0
The CYP2C19*17 allele is characterized by — CYP2C19 enzyme function
increased
-Unlike CYP2D6, the CYP2C19 RM and UM phenotypes are assigned in the presence of increased function alleles instead of having multiple copies of a gene.
Polymorphism in the promoter region of the CYP2C19 gene increases —
transcription
what are genotype definitions of UM compared to RM for CYP2C19
-UM: increased act compared to RM and have 2 increased fucn alleles.
-RM: inc act compared to NM but less than UM: has combinations of normal func and increased func alleles.
— allele frequencies are dependent on race and ethnicity
-which are the most common variants
-CYP2C19
- *2 and *3 alleles (principal nonfunctional alleles
)
CYP2C19 are present in the following races:
-*2 allele:
–% of Asians
–% of Caucasians and African Americans
-*3 allele:
–% of Asians
–% of Caucasians and African Americans
-PM phenotype
–% of Asians
–% of Caucasians and African Americans
-*2 allele:
30% of Asians
15% of Caucasians and African Americans
-*3 allele:
8% of Asians
less than 1% of Caucasians and African Americans
-PM phenotype
25% of Asians
~5% of Caucasians and African Americans
The CYP2C19 —— allele shares the same promoter region SNP as the increased function CYP2C19*17 allele (-806C>T)
no function *4B
It is important to test for — in addition to – to make an accurate CYP2C19 allele assignment
-1A>G (in *4B)
- -806C>T
the activity score system is used to assign CYP2C9 phenotypes
-NM: 2
-IM: 1 or 1.5
-PM: 0 or 0.5
Each CYP2C9 allele is assigned an activity value that will contribute to the final activity score number
-normal function 1
-decreased function 0.5
-no function 0
— enzymes are located both in the gut and the liver
-Patients who express the CYP3A5 gene are CYP3A5 – and – metabolizers.
-Patients who do not express the CYP3A5 gene are CYP3A5 – metabolizers
CYP3A5
-normal and intermediate
-poor
-It is common for individuals of – descent to express CYP3A5
enzymes.
-It is common for individuals of – descent NOT to have any
CYP3A5 enzymes (PM)
-African
-European
— phenotype is the low-risk phenotype: no dosage adjustments are required for patients with this phenotype.
— are the high-risk phenotypes
Dosing modifications may be necessary for certain medications for patients with these phenotypes
-CYP3A5 PM
-CYP3A5 IM and NM phenotypes
– polymorphisms have been associated with reduced glucuronidation in patients who have inherited decreased or no function variants
UGT1A1
— genotyping is used o diagnose Gilbert and Crigler-Najjar syndromes
UGT1A1
-– Gilbert syndrome
Decreased — activity (~30% of normal)
Patients who have – function variants (-,-,-)
– Crigler-Najjar syndrome (types 1 and 2)
Type 1: — of UGT1A1 activity
Type 2: — enzyme activity
– Gilbert syndrome
Decreased hepatic UGT1A1 activity (~30% of normal)
Patients who have two decreased function variants (*6, *28, *37)
– Crigler-Najjar syndrome (types 1 and 2)
Type 1: almost complete absence of UGT1A1 activity
Type 2: severely decreased but detectable UGT1A1 enzyme activity
