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Therapeutics 4 - Pharmacogenetics

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parkerliu's version from 2015-05-03 02:10

Allele Variants

AlleleResulting Activity
2C9*1Wild-Type
2C9*270-90% of Wild-Type
2C9*310-30% of Wild-Type
2C9*6Null-Variant
2C19*2/3Poor Metabolizer
2C19*4Null-Variant
2C19*17Ultra-Rapid Metabolizer
2D6*1/2Normal Function
2D6*10/17Reduced Function
2D6*3/4/5Null-Variant
UGT1A*1Normal
UGT1A*28Reduced Function
NAT2*4Rapid
NAT2*(non-4)Slow
SLCO1B1*1A/1BIncreased uptake
SLCO1B1*5/15/17Decreased uptake
VKORC1*2Decreased gene expression
VKORC1*3Increased gene expression
ADRB1 389Decreased sensitivity
ARDB1 49Increased Sensitivity
ARDB2 16Decreased Sensitivity
ARDB2 27Increased Sensitivity
HMGCR SNP 12/29Decreased effectiveness
HLA-B*5701Abacavir sensitivity
HLA-B*5801Allopurinol sensitivity
HLA-B*1502Phenytoin/Carbamazepine sensitivity
G6PD IVNormal
G6PD II or IIIDeficient
G6PD IDeficient with CNSHA
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Drug Interactions

Question Answer
2C9Warfarin, Phenytoin, NSAIDs, Sulfonylureas
2C19Clopidogrel, Diazepam, TCAs, PPIs
2D6Codeine and Derivatives, TCAs/SSRIs/Antipsychotics, DMX, Tramadol, Beta-blockers, antiarrhythmics, tamoxifen
UGTIrinotecan
NAT2Isoniazid, Hydralazine, Sulfasalazine
SLCO1B1Simvastatin
VKORWarfarin
ARDBBeta-agonist/blockers
HMGCRStatins
G6PDRasburicase, primaquine, sulfonylureas, dapsone
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Differences by Race(Defect leading to reduced function)

Question Answer
2D6Caucasian > African-American > Asian-American
2C19Asian-Americans >> African-Americans > Caucasian
SLCO1B1(decreased uptake)Caucasian = Asian-Americans > African-Americans
SLCO1B1(increased uptake)African-American > Asian-American > Caucasians
2C9Caucasian > African-American > Asian-American
UGTAfrican-Americans > Caucasians > Asian-Americans
NATCaucasian = African-American > Asian-American
VKORAsian-Americans=Decreased; African-Americans=Increased
HLA-B*5701Caucasian > Asian-Americans = African-Americans
HLA-B*5801Asian-Americans > Caucasians
HLA-B*1502Asian-Americans > Caucasians = African-Americans
G6PDAfrican-Americans > Caucasians = Asian-Americans
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