Gene polymorphisms and Pharmacogenomics Flashcards
What does Pharmacogenomics mean?
Influence of genetic variatioon on drug response correlating gene expression or SNP with drug toxicity
What does Microarray indentify polymorphisms in?
CYP450 genes
What are regions of chromosome in between genes termed?
Non-coding regions
What is transcription?
Generation fo RNA from a DNA template
What is an Exon?
Blocks of a gene whose DNA sequence will determine AA sequence
What is an Intron?
Blocks of a gene which dont code for protein and removed during transcript to generate mRNA
What is Translation?
Protein is made using mRNA as sequence
What is a Mutation?
Change in DNA sequence
What is a Nonsynonymous mutation?
Mutation that results in change of protein sequence
What is a Genotype?
Combo of allels for a given gene within indiv
What is a Haplotype?
Combo of SNP present at different genetic locations that are transmitted on same chromatid
How many mutations does your genome contain?
100 new
What are silent variations?
Some changes that occur in coding which no known effect
What is Haemophilia?
Simple disease in which variation in one gene causes disease
What are complex diseases?
Symptons seen only after many variations have occured in diff genes in same cell
What do SNPs act as?
Biological markers - help identify genes with disease
What is the Apoplipoprotein ApoE?
Associated with Alzheimers - has 2 SNPS
What are 3 Possible Alleles termed?
E2,3,4 different by 1 base in coding region
How to treat Breast cancer?
Trastuzumab
How to treat V600 B-Raf melanoma?
Vemurafenib
How do treat Chronic myelogenous leukaemia?
Imatinib
How do coagulation function?
Catalyses conversion of fluid blood to solid fibrin clot
What is Coagulation responsible for?
Making fibrous network wall at site of lesion
How does Coagulation work?
Trap exudate and foreing bodies, Stop bleeing by platelet plug, Provide framework for repair
What are coagulation factors?
Plasma proteins made in inactive form in liver activated at sites of vessel injury to active proteas
What are phospholipid factors?
On surface of activate platelets
What are Calcium ion factors?
Required for several coagu factors to be active
What does Fibrin do?
Give blood clot mechanical strength
What are 3 arms for coagulation factors?
Intrinsic, Extrinsic, Common
What are e.g of enhanced coagulaion in disease?
DVT, PE, MI,
Why is warfarin administered?
Patients with increased thrombotic tendency ; PE, DVT, AFib, Heart valve
What is the Warfarin mechanism?
VitK- co factor for GGCX in live required for calcium binding - vitamin k reductase antagonist
What are the Variable pharmacokinetics of warfarin?
Liver enzyme responsible for inactivation CYP2C9
VitK reductase VKORC1
How is Warfarin metabolised?
S isomer has more than 5 Fold , more potent, CYP450/2C9
What alleles impaired warfarin metabolism?
CYP2C9 2 +3 alleles on nonsynonymous variation
What is the Frequency of Warfarin on ethnic variation?
Caucasions - CYP2C9 2+3
Asians - Non-coding 1173C
