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

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.