The association of polymorphisms in related circadian rhythm genes and clopidogrel resistance susceptibility

Previous studies have confirmed that a dynamic change in circadian rhythm will affect platelet activity, resulting in clopidogrel resistance (CR). We attempted to evaluate whether polymorphisms of related circadian rhythm genes are involved in CR in stable coronary artery disease (SCAD) patients. A sum of 204 SCAD patients met our requirements and were recruited, and 96 patients were considered to have CR. After clinical data collection and platelet function evaluation, genomic DNA was isolated from human peripheral blood, and 23 tagSNPs from related circadian rhythm genes were genotyped by GenomeLab SNPstream Genotyping System. After RNA isolation, relative expression of related gene mRNAs (CLOCK, CRY1, CACNA1C and PRKCG) was measured by real-time PCR. The results showed that polymorphisms in CRY1, CACNA1C and PRKCG changed the response to clopidogrel. And then, the rs1801260 polymorphism might lead to higher mRNA expression in CLOCK and potentially induce the occurrence of CR. Additionally, the TC genotype of rs3745406 might lower mRNA expression of PRKCG, resulting in CR. These findings support the hypothesized role of circadian rhythm genes in CR and indicate probable biomarkers for CR susceptibility, providing new insight into individualized medicine for coronary heart disease.