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Genome-wide association study reveals a complex genetic architecture underpinning-induced CYP3A4 enzyme activity.

Rahmioglu, N, Heaton, J, Clement, G, Gill, R, Surdulescu, G, Zlobecka, K, Hodgkiss, D, Smith, NW and Ahmadi, KR (2013) Genome-wide association study reveals a complex genetic architecture underpinning-induced CYP3A4 enzyme activity. Eur J Drug Metab Pharmacokinet, 38 (1). pp. 63-67.

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Abstract

Atypical cytochrome P450 3A4 (CYP3A4) enzyme activity-induced and inhibited-is thought to be the driver of numerous poor or adverse therapeutic responses to up to 50 % of all commonly prescribed drugs. We carried out a genome-wide association study to identify common genetic variants associated with variation in induced CYP3A4 activity. A total of 310 twins were included in this study. Each participant had already completed a 14 days course of St John's Wort to induce CYP3A4, which was quantified through the metabolic ratio of exogenous 3-hydroxyquinine to quinine. We failed to detect any genome-wide significant associations (P < 1 × 10(-8)) with variation in induced CYP3A4 activity although several genomic regions were highlighted which may play minor roles. We report the first GWAS of variation in induced CYP3A4 activity and our preliminary results indicate a complex genetic architecture underpinning induced CYP3A4 enzyme activity.

Item Type: Article
Authors :
NameEmailORCID
Rahmioglu, NUNSPECIFIEDUNSPECIFIED
Heaton, JUNSPECIFIEDUNSPECIFIED
Clement, GUNSPECIFIEDUNSPECIFIED
Gill, RUNSPECIFIEDUNSPECIFIED
Surdulescu, GUNSPECIFIEDUNSPECIFIED
Zlobecka, KUNSPECIFIEDUNSPECIFIED
Hodgkiss, DUNSPECIFIEDUNSPECIFIED
Smith, NWUNSPECIFIEDUNSPECIFIED
Ahmadi, KRk.ahmadi@surrey.ac.ukUNSPECIFIED
Date : March 2013
Identification Number : https://doi.org/10.1007/s13318-012-0103-z
Uncontrolled Keywords : Aged, Aged, 80 and over, Biomarkers, Biotransformation, Cytochrome P-450 CYP3A, Enzyme Induction, Female, Genome-Wide Association Study, Genotype, Humans, Hydroxylation, Hypericum, Liver, Middle Aged, Phenotype, Plant Preparations, Quinidine, Quinine, Substrate Specificity, Twins
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:48
Last Modified : 17 May 2017 14:44
URI: http://epubs.surrey.ac.uk/id/eprint/825172

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