title: Genotype-phenotype correlation of cytochrome P450 2C9 polymorphism in Indian National Capital Region.
abstract: Identification of polymorphism of cytochrome P450 2C9 (CYP2C9) enzymes in different ethnic populations is important to understand the differences in clinical responses to drugs. This study determines the CYP2C9 genetic polymorphism in Indian National Capital Region and correlates the phenotype-genotype. Losartan (25 mg) was administered to 107 volunteers to assess CYP2C9 activity, and, on the basis of results, volunteers were categorized as rapid and poor metabolizers. Molecular typing of CYP2C9*1 (wild type), CYP2C9*2, and CYP2C9*3 (the most common variant) was carried out by single-base primer extension technology for 37 subjects, of which 9 were poor metabolizers, and 28 were rapid metabolizers. 14.28 % of the studied population was identified as poor metabolizer for the category of drugs metabolized by CYP2C9. Significant difference was observed between the mean ratio (drug/metabolite) of poor (11.38 ± 5.88) and rapid (1.18 ± 1.11) drug metabolizers. The study suggests that phenotyping of CYP2C9 is desirable before enrollment of subjects for clinical trials or for deciding drug dose regimen as 14.28 % of study population was found to be poor metabolizer for the category of drugs metabolized by CYP2C9. This study establishes phenotype-genotype correlation, and proposes to use genotyping or phenotyping to evaluate the status of drug metabolizing capacity of CYP2C9 as a primary screening procedure before enrolling subjects in clinical trials or in clinical practice.
authors: Department of Biochemistry, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India.
authors: Ekta
authors: E
authors: Varshney
authors: Nilanjan
authors: N
authors: Saha
authors: Monika
authors: M
authors: Tandon
authors: Vikesh
authors: V
authors: Shrivastava
authors: Shakir
authors: S
authors: Ali
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D002264:Carboxylic Acids / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9; D017931:DNA Primers; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D019808:Losartan / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D002264:Carboxylic Acids; D017931:DNA Primers; D004364:Pharmaceutical Preparations; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D019808:Losartan