Coding SNPs in hsa-miR-1343-3p and hsa-miR-6783-3p target sites of CYP2C19 modulates clopidogrel response in individuals with cardiovascular diseases

Publication date: Available online 28 January 2020Source: Life SciencesAuthor(s): Anu Radha Sharma, Manik Vohra, Vaibhav Shukla, Vasudeva Guddattu, Abdul Razak UK, Ranjan Shetty, Shashikiran Umakanth, Kapaettu Satyamoorthy, Padmalatha S. RaiAbstractAimsTo investigate the impact of microRNA target SNPs (mirSNPs) and their interaction with miRNAs on important drug-metabolizing enzymes, transporters and target genes for prediction of clopidogrel drug response in cardiovascular disease individuals.Main methodsA prospective cross-sectional study was conducted on 292 individuals undergoing clopidogrel drug therapy. All the enrolled participants were administered 300 mg loading dose followed by 75 mg dose of maintenance therapy. Platelet aggregations were measured before administration of the loading dose and 2 h post fifth day dose of clopidogrel maintenance therapy. Clopidogrel carboxylic acid metabolite from plasma and urine were analyzed post maintenance therapy using the RP-HPLC method. Genotyping of mirSNP's shortlisted through in silico analysis was performed by tetra ARMS PCR and validated by Sanger DNA sequencing. The levels of selected miRNAs were estimated by the TaqMan-PCR assay. Functional validation of mirSNPs was performed in HepG2 cells after transfecting with the selected gene and miRNA mimics. Protein expressions were analyzed by western blot.Key findings23% of enrolled individuals showed resistance to clopidogrel therapy. Out of 13 mirSNP's analyzed, CYP2C19...
Source: Life Sciences - Category: Biology Source Type: research