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Research Paper|Volume 12, Issue 24|pp 25684—25699

A SNP involved in alternative splicing of ABCB1 is associated with clopidogrel resistance in coronary heart disease in Chinese population

Shasha Zhang1, Jing Wang1, Anan Zhang4, Xiaowei Zhang5, Tao You6,7, Dingxiong Xie8, Wenke Yang1, Yuhong Chen3, Xuetian Zhang3, Cuixia Di3, Xiaodong Xie1,2
  • 1School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
  • 2Gansu Provincial Maternity and Childcare Hospital, Lanzhou 730050, China
  • 3Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
  • 4The Second Hospital of Lanzhou University, Lanzhou 730000, China
  • 5Department of Cardiology, The Second Hospital of Lanzhou University, Lanzhou 730000, China
  • 6Department of Cardiac Surgery, Gansu Provincial Hospital, Lanzhou 730000, China
  • 7Congenital Heart Disease Diagnosis and Treatment Gansu Province International Science and Technology Cooperation Base, Lanzhou 730000, China
  • 8Gansu Cardiovascular Institute, Lanzhou 730050, China
* Equal contribution
Received: July 2, 2020Accepted: September 22, 2020Published: November 20, 2020
https://doi.org/10.18632/aging.104177

Copyright: © 2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Although many scientists are studying the association between genetic polymorphism of ABCB1 and CR in patients, the molecular mechanism has not been further studied in patients with CHD. This study investigated the relationship between SNP of the ABCB1 gene in patients with CHD and CR, and whether the polymorphism of the ABCB1 gene affects the AS of the gene. 741 patients were enrolled in the study, 316 CR cases and 425 NCR cases. The correlation between CR risk and clinical-pathological characteristics were studied. Additionally, the five SNPs were analysed by PCR and Mass Array genotyping methods. Furthermore, silicon analysis was used to predict whether the polymorphism affects the process of AS. Results showed that there was a significant correlation between rs1045642 polymorphism and CR in genotyping and allele analysis. The rs1045642 polymorphism of the ABCB1 gene of CHD patients carrying the A allele are more likely to develop CR. Silicon analysis showed that rs1045642 generated a new ESE sequence which might affect AS of ABCB1 gene. We hypothesize that the mechanism of CR might be caused by a change in the AS caused by the polymorphism of the gene. Thus, this work provides guidance for the clinical use of clopidogrel.