Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, No. 248 East Street, Quanzhou, 362002, Fujian, China.
Department of Immunology, School of Basic Medical Sciences, Fujian Medical University, 1 Xue Fu North Road, Fuzhou, 350122, Fujian, China.
BMC Cardiovasc Disord. 2023 Jan 21;23(1):41. doi: 10.1186/s12872-023-03075-4.
The objective of this study was to investigate the relationship between P2Y1 and P2Y12 genotypes and the risk of acute myocardial infarction (AMI) in the Quanzhou population and to determine associations between P2Y1 and P2Y12 genotypes and ADP-induced platelet aggregation in this population.
All subjects were screened for P2Y1 (c.1622A > G) and P2Y12 (H1/H2, c.34C > T) polymorphisms by direct DNA sequencing. The maximal platelet aggregation rate (MAR) in AMI patients (n = 61) and healthy control subjects (n = 50) was measured by a PL-12 platelet function analyzer, and adenosine diphosphate (ADP) (5 μmol/L) was used as an agonist.
The haploid H2 allele in the P2Y12 gene was more frequent in patients with AMI than in control subjects (OR 1.887, P = 0.005). The P2Y12 H2 haplotype was significantly associated with AMI in the codominant (P = 0.008), dominant (OR 2.103, P = 0.003), and overdominant models (OR 2.133, P = 0.003). After adjusting for potential confounders, H2 haplotype carriers had a 2.132-fold increased risk for AMI (OR 2.132, P = 0.012) compared with noncarriers. Moreover, we observed that the ADP-induced MAR in the carriers of the H2 haplotype from the control group was somewhat higher than that in noncarriers of this group (P = 0.020). However, we failed to demonstrate that the P2Y1 H1/H2 polymorphism affected ADP-induced MAR in AMI patients. Additionally, P2Y1 c.1622A > and P2Y12 c.34C > T polymorphisms were not associated with the risk of AMI or ADP-induced MAR in either group.
Therefore, our results suggest that the P2Y12 H2 haplotype was associated with a higher risk of AMI, while its effect on increased ADP-induced platelet aggregation remains to be investigated. Thus, the P2Y12 H2 haplotype may be a potential marker for AMI.
本研究旨在探讨 P2Y1 和 P2Y12 基因型与泉州人群急性心肌梗死(AMI)风险的关系,并确定 P2Y1 和 P2Y12 基因型与该人群中 ADP 诱导的血小板聚集之间的关系。
通过直接 DNA 测序对所有受试者进行 P2Y1(c.1622A>G)和 P2Y12(H1/H2,c.34C>T)多态性筛查。采用 PL-12 血小板功能分析仪测量 AMI 患者(n=61)和健康对照者(n=50)的最大血小板聚集率(MAR),并使用二磷酸腺苷(ADP)(5μmol/L)作为激动剂。
与对照组相比,P2Y12 基因中的单倍型 H2 等位基因在 AMI 患者中更为常见(OR 1.887,P=0.005)。P2Y12 H2 单倍型在共显性(P=0.008)、显性(OR 2.103,P=0.003)和超显性模型(OR 2.133,P=0.003)中与 AMI 显著相关。调整潜在混杂因素后,与非携带者相比,H2 单倍型携带者发生 AMI 的风险增加 2.132 倍(OR 2.132,P=0.012)。此外,我们观察到,对照组 H2 单倍型携带者的 ADP 诱导的 MAR 略高于该组非携带者(P=0.020)。然而,我们未能证明 P2Y1 H1/H2 多态性影响 AMI 患者的 ADP 诱导的 MAR。此外,P2Y1 c.1622A>G 和 P2Y12 c.34C>T 多态性与两组人群的 AMI 风险或 ADP 诱导的 MAR 均无相关性。
因此,我们的结果表明 P2Y12 H2 单倍型与 AMI 风险增加相关,而其对 ADP 诱导的血小板聚集增加的影响仍有待研究。因此,P2Y12 H2 单倍型可能是 AMI 的潜在标志物。