Authors: Uppugunduri Satyanarayana Chakradhara Rao Anichavezhi Devendran Kapettu Satyamoorthy Deepak Gopal Shewade Rajgopal Krishnamoorthy Adithan Chandrasekaran
Publish Date: 2010/12/09
Volume: 38, Issue: 6, Pages: 4171-4179
Abstract
CYP2C19 is an enzyme involved in the metabolism of several clinically important drugs The variations in the CYP2C19 promoter region may alter the transcription of the gene by altering the interaction between the trans and cisacting elements In the present study CYP2C19 promoter region with different variant alleles were cloned into a pGL3 basic luciferase reporter vector and transfected into HepG2 cell lines Subsequently dual luciferase activity was measured to evaluate the activity of the promoter region Gel shift assays with predicted binding sites for CCAAT displacement protein activating transcription factor2 and glucocorticoid receptor were performed Results from this study indicate that few variations present in the putative cisacting elements of the CYP2C19 promoter region such as −1442TC −779AC and −98TC −1498TG and −828delT alter the transcription of the gene Specific binding with nuclear proteins was also observed in gel shift assays This may account for the interindividual variations in gene expression and genotype dependant differences in gene transcription The results also suggest the role of activating transcription factor2 and CCAAT displacement repressor protein on CYP2C19 gene transcriptionThe study was funded by Indian Council of Medical Research ICMR—Institut national de la santeá et de la recherche meá dicale INSERM collaborative research project ICMR sanction order no 50/6/2004 dated 05/10/06 A part of the study was also supported by JIPMER Institutional intramural research fund Edn71/2010 dated 04022010 We also thank Dr Surendiran for proof reading the article The technical assistance provided by Mr Rajan Sundaram is gratefully acknowledged
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