Dataset Information

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 dual-antiplatelet 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.

SUBMITTER: Zhong J

PROVIDER: S-EPMC8605143 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aims/introductionTo investigate the differential effects of maternal versus paternal history of diabetes on the risks for diabetes and prediabetes, as well as on insulin secretion and resistance in Chinese individuals.Materials and methodsFrom the 2007 to 2008 China National Diabetes and Metabolism Disorders Study, 39,244 participants were included and divided into four categories: negative parental history, paternal history only (PH), maternal history only (MH), and both paternal and maternal history.ResultsThe age- and sex-standardized prevalence rates of diabetes in the negative parental history, PH, MH, and both paternal and maternal history groups were 8.59, 12.56, 15.86 and 29.81%, respectively. The prevalence rates of impaired glucose metabolism were 24.13, 25.41, 31.13 and 50.80%, with the prevalence in the MH group being significantly higher than that in the PH group. Compared with that in the FH0 group, the risks of diabetes in the PH, MH, and both paternal and maternal history groups were 2.01-, 2.67- and 6.37-fold greater, and the risks of impaired glucose metabolism were 1.28-, 1.65- and 3.45-fold greater. In addition, MH had a significantly greater impact on impaired glucose metabolism than PH (PMHvsPH = 0.0292). Regression analyses suggested MH was associated with homeostatic model assessment for β-cell function (β[SE] = -0.0910[0.0334], P = 0.0065), insulinogenic index (-0.1866[0.0550], P = 0.0007), homeostatic model assessment for insulin resistance (0.0662[0.0227], P = 0.0036) and Matsuda Index [-0.0716(0.0203), P = 0.0004]. PH was specifically associated with homeostatic model assessment for insulin resistance (0.1343[0.0267], P < 0.0001) and Matsuda Index (-0.1566[0.0243], P < 0.0001), but the effects were stronger than those of MH (PMHvsPH = 0.0431, 0.0054).ConclusionsMH and PH differentially influence the risks for diabetes, insulin secretion, and insulin resistance in the Chinese population, suggesting they participate in the pathogenesis of diabetes through different mechanisms.