Term
| talking about a SINGLE GENE that gets mutated and will affect the drug response (ex: p53 tumor suppressor gene) |
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Definition
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Term
| study of inter-individual variation in the whole genome and looking at candidate gene SNP maps, haplotype markers, and alteration in gene expression or inactivation that may be correlated with pharmacological function or therapeutic response |
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Definition
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Term
| based on the whole genome, we have drugs that are targeted to certain genes and based on that gene sequence in a specific patient you can have a certain drug response in that patient |
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Definition
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Term
| You can see which genes are affected by which drugs and this helps to identify if there are differences in your specific patient to avoid side effects, etc |
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Definition
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Term
| Pharmacogenomics identifies biomarkers for diagnostic testing |
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Definition
| identifies responders for early txt, excludes non-responders to avoid toxicities, lifts financial burden, enriches clinical trials of novel therapeutics |
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Term
| defined as a variation in DNA sequence |
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Definition
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Term
| if DNA variation present in less than 1% of population |
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Definition
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Term
| if DNA variation present in more than 1% of population |
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Definition
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Term
| SNPs, > 1 nt change, entire gene insertion/deletion, or extra copies of a gene |
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Definition
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Term
| nomenclature: "VKORC2" from VKORC2 1173 C>T |
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Definition
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Term
| nomenclature: "1173" from VKORC2 1173 C>T |
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Definition
| indicates the nucleotide on the gene |
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Term
| nomenclature: "C" from VKORC2 1173 C > T |
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Definition
| represents the original (wild-type) nucleotide |
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Term
| nomenclature: "T" from VKORC2 1173 C > T |
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Definition
| represents the nucleotide that has changed to result in the SNP |
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Term
| single database for all genetic variation information |
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Definition
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Term
| the variant (and wild type) forms of a gene at a particular location on a chromosome |
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Definition
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Term
| each individual carries 2 alleles of each gene; the 2 alleles that any individual has |
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Definition
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Term
| set of alleles at multiple loci or areas of a gene that coexist on the same chromosome |
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Definition
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Term
| when a higher frequency of the set of alleles co-exist than would be predicted by random chance |
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Definition
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Term
| a single base substitution occurs within a gene; several million have been identified; may or may not alter protein synthesis |
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Definition
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Term
| substitution of one base for another in an exon of a gene coding for a protein, such that the produced amino acid sequence is not modified |
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Definition
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Term
| substitution of one base for another in an exon of a gene coding for a protein, such that the produced amino acid sequence is not modified |
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Definition
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Term
| a change in amino acid that may result in a conservative, semi-conservative or radical change to the protein wild-type |
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Definition
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Term
| proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains |
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Definition
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Term
| the carbohydrate is attached to the protein in a co-translational or posttranslational modification (glycoproteins) |
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Definition
| glycosylation (plays a role in cell-cell interactions) |
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Term
| Synonymous: SNP P-Glycoprotein (P-gp) affected drugs |
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Definition
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Term
| Non-synonymous: SNP TPMT affected drugs |
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Definition
| Azathioprine, 6-mercaptopurine |
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Term
| There is a decreased conversion of 6-MP to its inactive metabolite and results in an INCREASE of thioguanine nucleotides (6-TGN) an active metabolites which will affect efficacy and toxicity |
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Definition
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Term
| SNP CYP2C19 ---> CYP2C19*3 |
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Definition
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Term
| results in no enzyme activity |
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Definition
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Term
| Premature Stop Codon (CYP2C19*3) Affected Drugs |
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Definition
| Proton Pump Inhibitors (Omeprazole, Lansooprazole) |
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Term
| wild-type enzyme activity: cure rate of H. pylori for wild-type alleles is only around 20-30% due to a high metabolism of PPI into inactive metabolites |
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Definition
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Term
| with somewhat reduced enzyme activity there is a slight buildup of drug and the cure rate of H. pylori is about 50-60% |
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Definition
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Term
| major decrease in enzyme activity, resulting in a 14 fold increase in drug concentration and decreased metabolite concentration-- results in almost 100% cure rate of H. pylori |
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Definition
| CYP2C19 *2/*2 or *2/*3 or *3/*3 |
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Term
| Gene Deletion: CYP2D6 SNPs Affected Drugs |
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Definition
| SSRIs, tamoxifen, codeine, beta-blockers |
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Term
| not just a single nucleotide polymorphism, but thousands of nucleotide base pairs that comprise this gene are deleted |
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Definition
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Term
| Function effect for CYP2D6*5 |
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Definition
| Loss of function (or null activity); results in a poor metabolizer phenotype, the drug is not metabolized as well and there is buildup of these drugs in their system |
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Term
| Copy Number Variant -- extra copies of this gene are present |
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Definition
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Term
| With extra copies of the CYP2D6 gene |
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Definition
| more enzymes present to break down the drug |
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Term
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Definition
| ultra rapid metabolizer (UM) phenotype |
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Term
| CYP2D6*2XN affected drugs |
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Definition
| SSRIs, tamoxifen, codeine, beta-blockers |
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Term
| higher frequency of the CYP2C19*3 allele |
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Definition
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Term
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Definition
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Term
| Therapeutic Area Discussion Format |
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Definition
| patient case, gene/allele of interest, functional effect, population prevalence, clinical relevance, genome test/testing recommendation, patient case summary |
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Term
| human leukocyte antigen subclass B |
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Definition
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Term
| Functional effect of HLA-B*5701 |
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Definition
| high risk of abacavir-induced hypersensitivity reaction |
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Term
| highest prevalence of HLA-B*5701 (5-8%) |
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Definition
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Term
| can accurately predict patients who may be at risk for abacavir HSR |
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Definition
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Term
| showed similar trend in whites and blacks; accurately predicted 100% of abacavir HSR cases |
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Definition
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Term
| investigated HLA-B*5701 negative patients |
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Definition
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Term
| HLA typing: positive test for HLA-B*5701 |
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Definition
| confers an increased risk for HSR |
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