蛋白C-1641A/-1654C单倍型与脓毒症凝血功能的相关性研究

Correlation between protein C-1641A/-1654C haplotype and coagulation disorder in sepsis

目的探讨蛋白C -1641A/-1654C单倍型与中国汉族脓毒症患者凝血功能紊乱的相关性。方法采用直接测序法检测脓毒症患者蛋白C -1641A>G (rs1799809)和-1654C>T(rs1799808)位点的基因型, 分析其单倍型并根据单倍型分为两组, -1641A/-1654C(简称AC)单倍型携带者和非AC单倍型携带者。同时, 采用非配对t检验或Mann-WhitneyU检验进行分析, 比较两组间凝血/纤溶参数, 包括部分活化凝血活酶时间、凝血酶原时间、凝血酶原时间国际标准化比值、凝血酶时间、纤维蛋白原和D -二聚体等, 以及APC水平的差异。结果本研究共纳入174例脓毒症患者, 其中60例为AC单倍型携带者, 114例为非AC单倍型携带者。与非AC单倍型携带者相比, AC单倍型携带者的血小板计数明显减少, 部分活化凝血活酶时间明显延长, 蛋白C活化显著降低, 而其他凝血/纤溶参数包括凝血酶原时间、凝血酶原时间国际标准化比值、凝血酶时间、纤维蛋白原和D -二聚体差异无统计学意义。结论本研究发现蛋白C -1641A/-1654C单倍型导致脓毒症患者循环中的活化蛋白C水平降低、血小板计数减少, 部分活化凝血活酶时间延长。该结果表明, 脓毒症患者蛋白C -1641A/-1654C单倍型可能直接影响活化蛋白C水平, 进而导致脓毒症凝血功能紊乱。

Objective To investigate the correlation between protein C-1641A/-1654C haplotype and coagulation disorder in Chinese Han septic patients.Methods The genotypes of protein C gene-1641A>G(rs1799809)and-1654C>T(RS1799808)in septic patients were detected by direct sequencing,and their haplotypes were analyzed and divided into two groups according to the haplotype,-1641A/-1654C(AC)carriers and non-AC haplotype carriers.At the same time,unpaired t test or Mann-Whitney U test was used to compare the differences in coagulation/fibrinolytic parameters,including partial activated thrombin time,prothrombin time,internationally standardized ratio of prothrombin time,thrombin time,fibrinogen and D-dimer levels,as well as APC levels between the two groups.Results A total of 174 septic patients were included in this study,including 60 AC haplotype carriers and 114 non-AC haplotype carriers.Compared with non-AC haplotype carriers,AC haplotype carriers had significantly lower platelet'counts,significantly longer partial activated thrombin time,and significantly decreased activated protein C levels.Other coagulation/fibrinolytic parameters including prothrombin time,internationally standardized ratio of prothrombin time,thrombin time,fibrinogen and D-dimer were not significantly different between the two groups.Conclusions In this study,the protein C-1641A/-1654C haplotype was found to lead to decreased circulating activated protein C levels decreased platelet counts,and prolonged partial activated thrombin time in septic patients.These results suggest that the protein C-1641A/-1654C haplotype may directly affect the APC level and consequently influence the coagulation disorder of sepsis.