P-选择素基因多态性与可溶性P选择素浓度、心房颤动血栓栓塞的相关性研究

The association of soluble P-selectin gene polymorphisms with soluble P-selectin levels and thromboembolic events induced by atrial fibrillation

目的:探讨P选择素(P-selectin,PS)基因在2123C/G、1817T/C、Thr715Pro位点多态性与可溶性P选择素(soubleP-selectin,sPs)血清水平和心房颤动(房颤)血栓栓塞形成的相关性。方法:采用ELISA法对116例非瓣膜性房颤并发血栓栓塞患者(病例组)及129例非瓣膜性房颤患者(对照组)血浆sPs水平进行测定,并采用聚合酶链反应和限制性片断长度多态性,进行PS基因2123C/G、1817T/C、Thr715Pro位点多态性分析。结果:病例组sPs血清水平与对照组差异存在显著性[(42.4±8.2)μg/mLvs(36.3±8.4)μg/mL,P<0.001]。病例和对照组PS基因2123C/G位点基因型和等位基因分布差异均有显著性(P=0.007,P=0.009),1817T/C位点基因型和等位基因分布差异无显著性(P=0.384,P=0.169)。sPS血清水平与2123C/G基因多态性有明显相关性,GG基因型者的sPs血清水平显著高于GC+CC基因型(P<0.05),与1817T/C位点差异无显著性(P>0.05),未检测出Thr715Pro基因多态性。结论:PS基因多态性与循环sPs水平或血栓形成存在一定的关系,非瓣膜性房颤患者并发血栓形成可能存在遗传易感性。

Objective To investigate the association of the 2123C/G, 1817T/C, and Thr715Pro polymorphisms of soluble P-selectin （sP-selectin）with sP-selectin levels and thromboembolic events induced by nonvalvular atrial fibrillation （AF）. Methods Serum sP-selectin levels were detected in 116 patients with AF and thromboembolic events and in 129 with AF alone by ELISA. The 2123C/G, 1817T/C,and Thr715Pro polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Results There were statistical differences in sP-selectin levels between the patients with thromboembolic events and those with AF alone [ （42.4 ±8.2） μg/mL vs （36.3 ± 8.4）μg/mL, P 〈 0.001 ]. The distributions of genotype and allele of 2123C/G differed significantly between the groups （P = 0.007 and P = 0.009, respectively）, while no significant difference was found in 1817T/C （P = 0.384 and P = 0.169, respectively）, sP-selectin level was associated with the 2123C/G polymorphism but not with 1817T/ C allele （P 〉 0.05） ; it was markedly higher in the patients with GG genotype than in those carrying GC or CC genotype （P 〈 0.05）. No Thr715Pro polymorphism was detectable. Conclusions The sP-selectin gene polymorphisms are associated with serum sP-selectin levels or thromboembolic events, suggesting that the patients with nonvalvular AF and thromboembolic events may have genetic susceptibility.