ABCC2 p.Gly460Trp
| Predicted by SNAP2: | A: D (75%), C: D (75%), D: D (91%), E: D (91%), F: D (91%), H: D (91%), I: D (91%), K: D (91%), L: D (91%), M: D (91%), N: D (80%), P: D (91%), Q: D (80%), R: D (91%), S: D (80%), T: D (85%), V: D (85%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Pharmacogenetics-based new therapeutic concepts. Drug Metab Rev. 2004 Oct;36(3-4):617-38. Roots I, Gerloff T, Meisel C, Kirchheiner J, Goldammer M, Kaiser R, Laschinski G, Brockmoller J, Cascorbi I, Kleeberg U, Hildebrandt AG
Pharmacogenetics-based new therapeutic concepts.
Drug Metab Rev. 2004 Oct;36(3-4):617-38., [PMID:15554239]
Abstract [show]
Pharmacogenetics, one of the fields of clinical pharmacology, studies how genetic factors influence drug response. If hereditary traits are taken into account appropriately before starting drug treatment, the type of drug and its dosage can be tailored to the individual patient's needs. Pharmacogenetics adds a considerable amount of stringency to the doctor's therapeutic approach. Today, it is the relationship between dosage requirements and genetic variations in drug metabolizing enzymes like cytochrome P450 (CYP) 2D6 and CYP2C19, or in drug transporters like p-glycoprotein, that is substantiated best. A standard dose will bring about more adverse effects than usual if enzymatic activity is lacking or feeble. Sometimes, however, therapeutic response might be better due to higher concentrations: proton pump inhibitors for eradication of Helicobacter pylori are more efficacious in carriers of a deficient CYP2C19 variant. The drug's interaction with its target (e.g. receptor) also depends on genetic factors. In some cases genetic tests can help distinguish between responders and non-responders of a specific drug treatment. The first pharmacogenetic tests are already on the market.
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No. Sentence Comment
162 Recent studies on alpha-adducin e.g., demonstrated that the response to the antihypertensive agent hydrochlorothiazide is better in carriers of the gly460trp variation than in carriers of the wild-type allele (Cusi et al., 1997; Vormfelde et al., 2003).
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ABCC2 p.Gly460Trp 15554239:162:148
status: NEW176 GeneExampleClinicalconsequencesReference b2-adrenozeptorAlbuterol,isoproterenolBronchodilatationvariousincertain haplotypecombinations;tachyphylaxis, desensitisationbyagonistandeffect dependonvariant (Dishyetal.,2001; Drysdaleetal.,2000; Israeletal.,2000) Dopaminetransporter (9x40bpVNTR) L-DopaOccurrenceofpsychosisordyskinesia(Kaiseretal.,2003) 5-lipoxygenaseZileutonAsthmaticswhocarrythetandem-repeat promotervariantarenon-responders (Drazenetal.,1999) ApolipoproteinETacrinOnlyeffectiveinApoE4-negativpatients withM.Alzheimer (Poirieretal.,1995) MGMTAlkylatingagentsMethylationofpromoter,favorable therapeuticresultsinpatients withglioma (Estelleretal.,2000) KCNE2(T8AinMiRP1)Sulfamethoxazol, procainamide,oxatomide Drug-inducedlongQT-syndromein carriersofthevariant (Sestietal.,2000) GlycoproteinIIIa(PLA1 /A2 )Inhibitorsofthrombocyte aggregation (aspirin,abciximab) LesseffectiveincarriersofPLA2 (Cookeetal.,1998; Michelsonetal.,2000; Wheeleretal.,2002) CETP(B1/B2)PravastatinDevelopmentofarteriosclerosis slowerincarriersofB1B1 (Kuivenhovenetal.,1998) a-adducin(Gly460Trp)Hydrochlorothiazide(HCT)Carriersof460Gly/Tryshow betterresponsetoHCTin combinationwithsaltrestriction (Cusietal.,1997) ACE(I/D)EnalaprilatEfficacylongerandbetterincarriers ofgenotypeACE-I/I (Uedaetal.,1998) MGMT,O6 -methylguanin-DNAmethyltransferase;CETP,Cholesterolestertransferprotein;ACE,Angiotensin-convertingenzyme;VNTR,Variable numberoftandemrepeat. unsatisfactory antiemetic response.
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ABCC2 p.Gly460Trp 15554239:176:1069
status: NEW