CYP2C9 promoter region single-nucleotide polymorphisms linked to the R150H polymorphism are functional suggesting their role in CYP2C9*8-mediated effects
| Autor: | Kimberly Freeman, Danxin Wang, Shitalben R. Patel, Hyunyoung Jeong, David Vaynshteyn, Larisa H. Cavallari, Minoli A. Perera, Katrzyna Drozda, Harumi Takahashi |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Linkage disequilibrium Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Article Genotype Genetics medicine Humans General Pharmacology Toxicology and Pharmaceutics Allele Promoter Regions Genetic Molecular Biology CYP2C9 Alleles Genetic Association Studies Genetics (clinical) Aged Cytochrome P-450 CYP2C9 Dose-Response Relationship Drug Haplotype Warfarin Anticoagulants Promoter Middle Aged Molecular biology Black or African American Gene Expression Regulation Haplotypes Molecular Medicine Female Aryl Hydrocarbon Hydroxylases medicine.drug |
| Zdroj: | Pharmacogenetics and Genomics. 23:228-231 |
| ISSN: | 1744-6872 |
| Popis: | Cytochrome P450 2C9 (CYP2C9) c.449G> A (*8) is common in African Americans and is associated with decreased warfarin clearance. We examined the effect of promoter region variants inherited with 449G > A on warfarin clearance, dose requirements, and CYP2C9 expression. In an African American cohort, 449G > A was in linkage disequilibrium with c. – 1766T >C (r2 = 0.89) and c. – 1188T>C (D′ =1). The combination of the – 1766C and 449A alleles with the – 1188CC genotype was associated with lower S-warfarin clearance (0.86±0.22 vs. 1.66±0.75 ml/min/m2; n=48; P A decrease CYP2C9 expression and contribute to CYP2C9*8 effects on warfarin clearance and dose requirements. |
| Databáze: | OpenAIRE |
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