Molekulargenetisches Labor
Zentrum für Nephrologie und Stoffwechsel
Moldiag Erkrankungen Gene Support Kontakt

Genetische Einflüsse auf Arzneimittel-Verträglichkeit

Pharmakogenetik untersucht die individuelle Verträglichkeit verschiedener Medikamente. Das Ziel besteht in einer optimal individuell angepassten Therapie, um höchste Effektivität der medikamentösen Therapie und beste Verträglichkeit zu erreichen.

Gliederung

Genetisch bedingte Erkrankungen
Erbliche Augenerkrankungen und Sehstörungen
Erbliche Blutkrankheiten und Gerinnungsstörungen
Erbliche Bronchial- und Lungenerkrankungen
Erbliche Erkrankungen des Muskel- und Skelettsystems
Erbliche Erkrankungen im Hals-Nasen-Ohren-Bereich
Erbliche Fehlbildungen
Erbliche Gefäßerkrankungen
Erbliche Hauterkrankungen
Erbliche Herzerkrankungen
Erbliche Infektionsanfälligkeiten
Erbliche Lebererkrankungen
Erbliche Nervenerkrankungen
Erbliche Nierenerkrankungen
Erbliche Pankreaserkrankungen
Erbliche Stoffwechselerkrankungen
Erbliche Tumorerkrankungen
Erbliche endokrinologische Erkrankungen
Erbliche immunologische Erkrankungen
Erblicher Bluthochdruck
Genetische Einflüsse auf Arzneimittel-Verträglichkeit
Coumarin-Resistenz
CYP2A6
CYP2C9
CYP4F2
VKORC1
Hepatitis C-Therapieansprechbarkeit
IFNG
Störungen im Cytochrom P450-System
CYP1A2
CYP2A6
CYP2C9
CYP2D6
CYP3A4
CYP4F2
Siponimod-Intoleranz
CYP2C9

Referenzen:

1.

Trask B et al. (1993) Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers.

external link
2.

Yamano S et al. (1990) The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes.

external link
3.

Wood AW et al. (1974) Genetic variation in coumarin hydroxylase activity in the mouse (Mus musculus).

external link
4.

Lush IE et al. (1978) Genetic variation between mice in their metabolism of coumarin and its derivatives.

external link
5.

London SJ et al. (1999) Genetic variation of CYP2A6, smoking, and risk of cancer.

external link
6.

Oscarson M et al. (1999) Characterisation and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population.

external link
7.

Paolini M et al. (1999) Co-carcinogenic effect of beta-carotene.

external link
8.

Miyamoto M et al. (1999) CYP2A6 gene deletion reduces susceptibility to lung cancer.

external link
9.

Gu DF et al. (2000) The use of long PCR to confirm three common alleles at the CYP2A6 locus and the relationship between genotype and smoking habit.

external link
10.

Hoffman SM et al. (2001) Organization, structure and evolution of the CYP2 gene cluster on human chromosome 19.

external link
11.

Daigo S et al. (2002) A novel mutant allele of the CYP2A6 gene (CYP2A6*11 ) found in a cancer patient who showed poor metabolic phenotype towards tegafur.

external link
12.

Oscarson M et al. (2002) Characterization of a novel CYP2A7/CYP2A6 hybrid allele (CYP2A6*12) that causes reduced CYP2A6 activity.

external link
13.

Saito S et al. (2003) Catalog of 680 variations among eight cytochrome p450 ( CYP) genes, nine esterase genes, and two other genes in the Japanese population.

external link
14.

OMURA T et al. (1964) THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE.

external link
15.

Gambier N et al. (2005) Association of CYP2A6*1B genetic variant with the amount of smoking in French adults from the Stanislas cohort.

external link
16.

Palmer G et al. (1991) Nomenclature Committee of the International Union of Biochemistry (NC-IUB). Nomenclature of electron-transfer proteins. Recommendations 1989.

external link
17.

None (1991) Proposed role of drug-metabolizing enzymes: regulation of steady state levels of the ligands that effect growth, homeostasis, differentiation, and neuroendocrine functions.

external link
18.

Mwenifumbo JC et al. (2008) Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent.

external link
19.

Miles JS et al. (1990) Close linkage of the cytochrome P450IIA gene subfamily (Cyp2a) to Cyp2b and Coh on mouse chromosome 7.

external link
20.

None (1979) Multiple forms of inducible drug-metabolizing enzymes: a reasonable mechanism by which any organism can cope with adversity.

external link
21.

Matsunaga T et al. (1990) Structure and in vitro transcription of the rat CYP2A1 and CYP2A2 genes and regional localization of the CYP2A gene subfamily on mouse chromosome 7.

external link
22.

Miles JS et al. (1989) Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity.

external link
23.

Yamano S et al. (1989) cDNA and deduced amino acid sequences of human P450 IIA3 (CYP2A3).

external link
24.

Negishi M et al. (1989) Mouse steroid 15 alpha-hydroxylase gene family: identification of type II P-450(15)alpha as coumarin 7-hydroxylase.

external link
25.

Phillips IR et al. (1985) A cytochrome P-450 gene family mapped to human chromosome 19.

external link
26.

Nebert DW et al. (1987) P450 genes: structure, evolution, and regulation.

external link
27.

Davis MB et al. (1986) Regional localization of a human cytochrome P-450 (CYP1) to chromosome 19q13.1-13.3.

external link
28.

None (1987) Linkage between the loci for peptidase D and cytochrome P-450 (CYP1) on chromosome 19.

external link
29.

Phillips IR et al. (1985) Isolation and sequence of a human cytochrome P-450 cDNA clone.

external link
30.

Wainwright BJ et al. (1985) RFLP for a human cytochrome P-450 gene at 19q13.1-qter (HGM8 provisional designation CYPI).

external link
31.

Fernandez-Salguero P et al. (1995) A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles.

external link
32.

Nelson DR et al. () The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature.

external link
33.

Aida K et al. (1994) Lack of the steroid 15 alpha-hydroxylase gene (Cyp2a-4) in wild mouse strain Mus spretus: rapid evolution of the P450 gene superfamily.

external link
34.

Nakajima M et al. (1996) Role of human cytochrome P4502A6 in C-oxidation of nicotine.

external link
35.

Hadidi H et al. (1997) A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin.

external link
36.

Yokoi T et al. (1998) Genetic polymorphism of drug metabolizing enzymes: new mutations in CYP2D6 and CYP2A6 genes in Japanese.

external link
37.

None (1976) Coumarin-7-hydroxylase activity in microsomes from needle biopsies of normal and diseased human liver.

external link
38.

Pianezza ML et al. (1998) Nicotine metabolism defect reduces smoking.

external link
39.

Oscarson M et al. (1998) Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase.

external link
40.

Kleinbloesem CH et al. (1984) Variability in nifedipine pharmacokinetics and dynamics: a new oxidation polymorphism in man.

external link
41.

Idle JR et al. (2000) Medical implications of HGP's sequence of chromosome 22.

external link
42.

Nakamura K et al. (2002) CYP2D6.10 present in human liver microsomes shows low catalytic activity and thermal stability.

external link
43.

Nelson DR et al. (2004) Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants.

external link
44.

Gasche Y et al. (2004) Codeine intoxication associated with ultrarapid CYP2D6 metabolism.

external link
45.

Gaedigk A et al. (1991) Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism.

external link
46.

Koren G et al. (2006) Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother.

external link
47.

Desmeules J et al. (1991) Impact of environmental and genetic factors on codeine analgesia.

external link
48.

Gough AC et al. (1990) Identification of the primary gene defect at the cytochrome P450 CYP2D locus.

external link
49.

Hanioka N et al. (1990) The human CYP2D locus associated with a common genetic defect in drug oxidation: a G1934----A base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3' splice recognition site.

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50.

Kagimoto M et al. (1990) Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes.

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51.

Chen X et al. (1995) The CYP2D6B allele is associated with a milder synaptic pathology in Alzheimer's disease.

external link
52.

Johansson I et al. (1993) Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine.

external link
53.

Panserat S et al. (1994) DNA haplotype-dependent differences in the amino acid sequence of debrisoquine 4-hydroxylase (CYP2D6): evidence for two major allozymes in extensive metabolisers.

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54.

Saxena R et al. (1994) Identification of a new variant CYP2D6 allele with a single base deletion in exon 3 and its association with the poor metabolizer phenotype.

external link
55.

Broly F et al. (1995) A nonsense mutation in the cytochrome P450 CYP2D6 gene identified in a Caucasian with an enzyme deficiency.

external link
56.

Steen VM et al. (1995) Homologous unequal cross-over involving a 2.8 kb direct repeat as a mechanism for the generation of allelic variants of human cytochrome P450 CYP2D6 gene.

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57.

Marez D et al. (1997) Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution.

external link
58.

Yue QY et al. (1997) Quantification of the O- and N-demethylated and the glucuronidated metabolites of codeine relative to the debrisoquine metabolic ratio in urine in ultrarapid, rapid, and poor debrisoquine hydroxylators.

external link
59.

Guengerich FP et al. (1986) Human-liver cytochromes P-450 involved in polymorphisms of drug oxidation.

external link
60.

Gough SM et al. (2003) Refined physical map of the human PAX2/HOX11/NFKB2 cancer gene region at 10q24 and relocalization of the HPV6AI1 viral integration site to 14q13.3-q21.1.

external link
61.

Tate SK et al. (2005) Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin.

external link
62.

Kohn MH et al. (2000) A gene-anchored map position of the rat warfarin-resistance locus, Rw, and its orthologs in mice and humans.

external link
63.

et al. (2009) Estimation of the warfarin dose with clinical and pharmacogenetic data.

external link
64.

Aithal GP et al. (1999) Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications.

external link
65.

Kidd RS et al. (1999) Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele.

external link
66.

Thum T et al. (2000) Gene expression in distinct regions of the heart.

external link
67.

Aithal GP et al. (2000) Relationship of polymorphism in CYP2C9 to genetic susceptibility to diclofenac-induced hepatitis.

external link
68.

Xie HG et al. (2001) Molecular basis of ethnic differences in drug disposition and response.

external link
69.

Leung AY et al. (2001) Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients.

external link
70.

Higashi MK et al. (2002) Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy.

external link
71.

Williams PA et al. (2003) Crystal structure of human cytochrome P450 2C9 with bound warfarin.

external link
72.

Kirchheiner J et al. (2003) Influence of CYP2C9 genetic polymorphisms on pharmacokinetics of celecoxib and its metabolites.

external link
73.

Fichtlscherer S et al. (2004) Inhibition of cytochrome P450 2C9 improves endothelium-dependent, nitric oxide-mediated vasodilatation in patients with coronary artery disease.

external link
74.

King BP et al. (2004) Upstream and coding region CYP2C9 polymorphisms: correlation with warfarin dose and metabolism.

external link
75.

Sanderson S et al. (2005) CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis.

external link
76.

Li T et al. (2006) Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation.

external link
77.

Gray IC et al. (1995) A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24.

external link
78.

Steward DJ et al. (1997) Genetic association between sensitivity to warfarin and expression of CYP2C9*3.

external link
79.

Caldwell MD et al. (2008) CYP4F2 genetic variant alters required warfarin dose.

external link
80.

Yuan HY et al. (2005) A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity.

external link
81.

Lessard E et al. (1997) Role of CYP2D6 in the N-hydroxylation of procainamide.

external link
82.

Lessard E et al. (1999) Involvement of CYP2D6 activity in the N-oxidation of procainamide in man.

external link
83.

Lindberg RL et al. (1992) Molecular characterization of the murine Coh locus: an amino acid difference at position 117 confers high and low coumarin 7-hydroxylase activity in P450coh.

external link
84.

O'REILLY RA et al. (1964) HEREDITARY TRANSMISSION OF EXCEPTIONAL RESISTANCE TO COUMARIN ANTICOAGULANT DRUGS. THE FIRST REPORTED KINDRED.

external link
85.

Shikata E et al. (2004) Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity.

external link
86.

Rost S et al. (2004) Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2.

external link
87.

Takahashi H et al. (2006) Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African-Americans.

external link
88.

Cooper GM et al. (2008) A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose.

external link
89.

Limdi NA et al. (2008) VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans.

external link
90.

Borgiani P et al. (2009) CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population.

external link
91.

Takeuchi F et al. (2009) A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose.

external link
92.

Nebert DW et al. () The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature.

external link
93.

Alving BM et al. (1985) Hereditary warfarin resistance. Investigation of a rare phenomenon.

external link
94.

Vesell ES et al. (1968) Genetic control of dicumarol levels in man.

external link
95.

None (1970) The second reported kindred with hereditary resistance to oral anticoagulant drugs.

external link
96.

Pool JG et al. (1968) Warfarin resistance in the rat.

external link
97.

Lewis RJ et al. (1967) Warfarin resistance.

external link
98.

Greavses JH et al. (1967) Heritable resistance to warfarin in rats.

external link
99.

Whitlon DS et al. (1978) Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition.

external link
100.

Tucker GT et al. (1977) Polymorphic hydroxylation of debrisoquine.

external link
101.

Heim MH et al. (1992) Evolution of a highly polymorphic human cytochrome P450 gene cluster: CYP2D6.

external link
102.

Heim M et al. (1990) Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplification.

external link
103.

Kimura S et al. (1989) The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene.

external link
104.

Matsunaga E et al. (1989) The CYP2D gene subfamily: analysis of the molecular basis of the debrisoquine 4-hydroxylase deficiency in DA rats.

external link
105.

Skoda RC et al. (1988) Two mutant alleles of the human cytochrome P-450db1 gene (P450C2D1) associated with genetically deficient metabolism of debrisoquine and other drugs.

external link
106.

Gonzalez FJ et al. (1988) Characterization of the common genetic defect in humans deficient in debrisoquine metabolism.

external link
107.

Gonzalez FJ et al. (1988) Human debrisoquine 4-hydroxylase (P450IID1): cDNA and deduced amino acid sequence and assignment of the CYP2D locus to chromosome 22.

external link
108.

Eichelbaum M et al. (1987) Chromosomal assignment of human cytochrome P-450 (debrisoquine/sparteine type) to chromosome 22.

external link
109.

Gonzalez FJ et al. (1987) Debrisoquine 4-hydroxylase: characterization of a new P450 gene subfamily, regulation, chromosomal mapping, and molecular analysis of the DA rat polymorphism.

external link
110.

Harmer D et al. (1986) The relationship between the acetylator and the sparteine hydroxylation polymorphisms.

external link
111.

Eichelbaum M et al. (1986) The genetic polymorphism of sparteine metabolism.

external link
112.

Nebert DW et al. (1987) The P450 gene superfamily: recommended nomenclature.

external link
113.

Eichelbaum M et al. (1985) Inter-ethnic difference in sparteine oxidation among Ghanaians and Germans.

external link
114.

Distlerath LM et al. (1984) Characterization of a human liver cytochrome P-450 involved in the oxidation of debrisoquine and other drugs by using antibodies raised to the analogous rat enzyme.

external link
115.

Dahl ML et al. (1995) Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis.

external link
116.

Agúndez JA et al. (1995) Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population.

external link
117.

Mura C et al. (1993) DNA haplotype dependency of debrisoquine 4-hydroxylase (CYP2D6) expression among extensive metabolisers.

external link
118.

Johansson I et al. (1994) Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation.

external link
119.

Bertilsson L et al. (1993) Molecular basis for rational megaprescribing in ultrarapid hydroxylators of debrisoquine.

external link
120.

Gough AC et al. (1993) Localization of the CYP2D gene locus to human chromosome 22q13.1 by polymerase chain reaction, in situ hybridization, and linkage analysis.

external link
121.

Daly AK et al. (1996) Nomenclature for human CYP2D6 alleles.

external link
122.

Nelson DR et al. (1996) P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature.

external link
123.

None (1997) Polymorphisms in drug-metabolizing enzymes: what is their clinical relevance and why do they exist?

external link
124.

Sachse C et al. (1997) Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences.

external link
125.

McLellan RA et al. (1997) Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians.

external link
126.

Tyndale RF et al. (1997) Genetically deficient CYP2D6 metabolism provides protection against oral opiate dependence.

external link
127.

Mikus G et al. (1998) Relevance of deficient CYP2D6 in opiate dependence.

external link
128.

Lundqvist E et al. (1999) Genetic mechanisms for duplication and multiduplication of the human CYP2D6 gene and methods for detection of duplicated CYP2D6 genes.

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129.

Bathum L et al. (1998) Ultrarapid metabolism of sparteine: frequency of alleles with duplicated CYP2D6 genes in a Danish population as determined by restriction fragment length polymorphism and long polymerase chain reaction.

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130.

Tateishi T et al. (1999) Analysis of the CYP2D6 gene in relation to dextromethorphan O-demethylation capacity in a Japanese population.

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131.

Brown MA et al. (2000) Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis.

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132.

Payami H et al. (2001) Parkinson's disease, CYP2D6 polymorphism, and age.

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133.

Elbaz A et al. (2004) CYP2D6 polymorphism, pesticide exposure, and Parkinson's disease.

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134.

Deng Y et al. (2004) Further evidence that interactions between CYP2D6 and pesticide exposure increase risk for Parkinson's disease.

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135.

Liou YH et al. (2006) The high prevalence of the poor and ultrarapid metabolite alleles of CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5 in Taiwanese population.

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136.

Pilotto A et al. (2009) Effect of a CYP2D6 polymorphism on the efficacy of donepezil in patients with Alzheimer disease.

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137.

Schroth W et al. (2009) Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen.

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138.

Sullivan-Klose TH et al. (1996) The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism.

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139.

None (2001) Racial differences in the response to drugs--pointers to genetic differences.

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140.

Maekawa K et al. (2006) Four novel defective alleles and comprehensive haplotype analysis of CYP2C9 in Japanese.

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141.

Speed WC et al. (2009) Global variation in CYP2C8-CYP2C9 functional haplotypes.

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142.

Ross KA et al. (2010) Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements.

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143.

Shurin SB et al. (2008) Pharmacogenomics--ready for prime time?

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Update: 14. August 2020
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