MirSNPs in Clopidogrel Metabolism Genes Predict Cardiovascular Disease Risk: A Case–Control Study And Meta-Analysis

Abstract

Aim: The present study was conducted to decipher the inter-relationship of SNPs and miRNAs involved in pharmacogenomics of clopidogrel on predisposition to cardiovascular diseases (CVDs). Materials & methods: A case–control study was conducted on 410 cases and 386 controls to analyze the association of 13 mirSNPs on CVDs risk. Genotyping was performed by tetra-primer amplification refractory mutation system PCR and validated using Sanger DNA sequencing. miRNA expression analysis was performed using TaqMan assays. A meta-analysis was performed for PON1 rs662 with coronary artery disease. Results & conclusion:PON1 rs662, PON1 rs3917577, CYP3A5 rs15524, COL4A1 rs874204 and PTGIR rs1126510 polymorphisms showed association with CVDs. The miRNA hsa-miR-224-5p showed differential expression in the PON1 rs3917577 GG genotype. The meta-analysis showed the population-specific impact of PON1 rs662 on South Asian and Middle East populations.

Keywords::

• cardiovascular diseases
• meta-analysis
• miRNAs
• mirSNPs
• PON1

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/pgs-2020-0110

Author contributions

AR Sharma, S Umakanth, K Satyamoorthy and PS Rai conceived the study. AR Sharma and S Patagi performed the experiments. AR Sharma analyzed the data. A Razak, R Shetty and S Umakanth provided the clinical samples and details. S Umakanth, K Satyamoorthy and PS Rai supervised the research, and ensured compliance with ethical and regulatory requirements for enrolled participants. AR Sharma wrote the manuscript. S Umakanth, K Satyamoorthy and PS Rai revised and finalized the manuscript. All the authors have read and approved the final manuscript.

Financial & competing interests disclosure

The study was supported by Indian Council of Medical Research (ICMR) (no. 3/1/2(16)/CVD/2018-NCD-II), Technology Information Forecasting and Assessment Council-Centre of Relevance and Excellence (TIFAC-CORE) in Pharmacogenomics, Dr. TMA Pai Endowment Chair in Pharmacogenomics, Manipal Academy of Higher Education, Manipal, DST-FIST, Government of India and K-FIST, Government of Karnataka. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Availability of data & material

All the data generated during the present work are available with the corresponding author and will be provided on reasonable request.

Ethical conduct of research

The current study and protocols were reviewed and approved by the Institutional Ethics Committee, Kasturba Medical College, MAHE, Manipal (IEC 107/2016). The participants were recruited after elucidating the study procedures and written informed consent was obtained. The Institutional Ethical Committee, Kasturba Hospital, Manipal reviewed and approved the methods which were in accordance with the relevant guidelines and regulations. Written informed consent was obtained from all the participants.

Additional information

Funding

The study was supported by Indian Council of Medical Research (ICMR) (no. 3/1/2(16)/CVD/2018-NCD-II), Technology Information Forecasting and Assessment Council-Centre of Relevance and Excellence (TIFAC-CORE) in Pharmacogenomics, Dr. TMA Pai Endowment Chair in Pharmacogenomics, Manipal Academy of Higher Education, Manipal, DST-FIST, Government of India and K-FIST, Government of Karnataka. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.