Gene polymorphisms of insulin secretion signaling pathway associated with clopidogrel resistance in Han Chinese population

Abstract

Background: Due to the loss of responsiveness to insulin, diabetes mellitus (DM) patients develop increased platelet reactivity and reduced response to antiplatelet agents. Nevertheless, the relationship between the single-nucleotide polymorphisms (SNP) of the signal pathway gene of insulin secretion and the effect of clopidogrel is elusive.Methods: Blood samples were collected from patients administered with dualantiplatelet therapy (clopidogrel, 75 mg, once daily and aspirin, 100 mg, once daily) after 5 days and completed test within 4 h. The VerifyNow P2Y12 assay was used to measure the platelet functions, and the results were expressed as a P2Y12 reaction unit (PRU). Notably, the selected SNPs were analyzed to demonstrate the functionality of genetic variants.Results: Analysis of the study population showed that old age, lower plasma albumin (ALB) level, higher creatinine (CREA) level, higher uric acid (UA) level, lower platelet (PLT) count, and lower plateletcrit (PCT) potentially increased the risk of clopidogrel resistance. In a single-nucleotide polymorphism rs6056209 of the PCLB1 gene, the AG genotype was a risk factor for clopidogrel resistance (p < 0.05, OR = 1.574).Similarly, the CC and AG genotype in GNAS rs7121 and CCKAR rs1800857 were protective factors (p < 0.05, OR = 0.094; p <0.05, OR = 0.491). TT was a protective factor in rs10814274 of the CREB3 gene (p < 0.05, OR = 0.444). In the RAPGEF4 gene polymorphism rs17746510, TG was the protective genotype, and the TT genotype was a risk factor for clopidogrel resistance. GCG rs5645 was confirmed; there was a relationship between genotypes containing A or G and clopidogrel resistance. Conclusion:Single-nucleotide polymorphisms of insulin secretion signaling pathway genes trigger clopidogrel resistance.

Metabolic remodeling of glycerophospholipids acts as a signature of dulaglutide and liraglutide treatment in recent-onset type 2 diabetes mellitus

“…GLP-1RAs may target these proteins, as shown in Table 3 . GLP1R, GNAS, and GCG were related to insulin resistance, which were verified by the previous studies ( 45 ). Recently, Yulia A et al.…”

Assessment of Risk Factors for Drug Resistance of Dual Anti Platelet Therapy After PCI

“…27 Platelet counts showed important differences among clopidogrel-resistant patients, which is in agreement with our findings; lower platelet counts were found to be associated with increased clopidogrel resistance in Han Chinese population. 32 However, Uzun et al verified that a higher platelet count is an independent factor of clopidogrel resistance in 207 PCI patients from Turkey; 26 Marginean et al reported similar findings in a study conducted in Romania. Whether or not racial differences contributed to the difference remains unknown.…”

Rare Variants of Obesity-Associated Genes in Young Adults with Abdominal Obesity

“…Allele A of the rs5645 was found by us in 11 heterozygous carriers. This variant was previously described as being associated with clopidogrel treatment resistance in the Han Chinese population [63].…”

“…The missense variant rs150179526 was identified in five patients with hyperlipidemia and hyperglycemia (Table 8). [63] VarSome (benign) * an association is reported in the literature.…”