DNA methylation mediates the genetic variants on ticagrelor major metabolite elimination and platelet function recovery after ticagrelor discontinuation-Reference-Cited by-同舟云学术

DNA methylation mediates the genetic variants on ticagrelor major metabolite elimination and platelet function recovery after ticagrelor discontinuation

Published:2022-05 Issue:10 Volume:14 Page:601-613
ISSN:1750-1911
Container-title:Epigenomics
language:en
Short-container-title:Epigenomics

Author:

Xu Guifeng¹²^ORCID,Liu Ju-E¹,Liu Xiaoqi¹,Zhong Wanping³,Wang Zixian³,Li Hanping³,Xiao Xiao¹,Chen Jiyan⁴,Zhong Shilong¹³,Lai Weihua¹

Affiliation:

1. Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, P.R. China

2. School of Medicine, South China University of Technology, Guangzhou, 510080, P.R. China

3. Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P.R. China

4. Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, 510080, P.R. China

Abstract

Aim: To investigate the influence of DNA methylation on ticagrelor major metabolite M8 elimination and platelet function recovery after ticagrelor discontinuation. Materials & methods: Among healthy Chinese subjects, a causal inference test was conducted to identify CpG sites located on absorption, distribution, metabolism and excretion genes that mediate genetic variants on M8 elimination. Colocalization analysis was used to identify the CpG sites that shared causal variants with platelet function recovery. Results: cg05300248 ( CHST9), cg05640674 ( SLC22A5) and cg00846580 ( DHRS7) mediated genetic variants on the M8 elimination. cg06338150 ( NOTCH1) and cg17456097 ( RPS6KA1) were demonstrated to have strong evidence of colocalization with platelet function recovery. Conclusion: The results provide new biological insights into the impact of DNA methylation on M8 elimination and platelet function recovery after ticagrelor discontinuation. Clinical trial registration: clinicaltrials.gov , identifier: NCT03092076

Funder

The Key-Area Research and Development Program of Guangdong Province, China

Science and Technology Development Projects of Guangdong, China

National Natural Science Foundation of China

Science and Technology Development Projects of Guangzhou, Guangdong, China

Excellent Young Talent Program of GDPH, China

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

Link

https://www.futuremedicine.com/doi/pdf/10.2217/epi-2021-0461

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