上海地区汉族人群蛋白C基因多态性与血浆蛋白C水平及肺血栓栓塞症发病风险的研究

目的 探讨蛋白C(PC)基因调控区3个位点的单核苷酸多态性及其构成的单倍体型与血浆PC水平及上海汉族人群肺血栓栓塞症(PTE)发病的相关性.方法 采用病例对照的研究方法,应用PCR-DNA直接测序法,在110例PTE患者和100名健康对照者中,对PC基因启动子区域的-1654C/T、-1641A/G以及5'-非翻译区-1476A/T位点多态性进行基因分型,血浆PC含量检测采用ELISA法.结果 ①PTE病例组合并有其他疾病及手术史发生率高于对照组(P＜0.01或P＜0.05),而在血栓栓塞家族史、心血管疾病家族史、外伤史、口服避孕药史、吸烟和饮酒史方面,两组之间差异无统计学意义.②两研究组间的PC基因-1654C/T位点的基因型分布无差异,而T等位基因频率在病例组相对较高,C等位基因频率则在对照组中较高,差异有统计学意义(P=0.021);而-1641A/G和-1476A/T位点的各基因型分布和其各自的等位基因频率在两组之间差异无统计学意义.③单倍体型分析显示,PC基因这三个多态性位点主要组成3种单倍体型,从主到次为-1654T/-1641A/-1476A、-1654C/-1641A/-1476A和-1654C/-1641G/-1476T,其中单倍体型TAA和CAA的频率分布在两组之间存在差异(P=0.021和P=0.043).④血浆PC含量的检测发现携带有TAA同时又未携带CAA者的血浆PC含量较携带有CAA同时未携带TAA者的血浆PC含量要低,但两组之间未达到显著性的差异.结论 PC基因调控区的位点多态性可能与上海汉族人群PTE的发病有关,但其是否为导致血浆PC水平高低的主要因素,有待进一步的证实.

Abstract：

Objective To investigate the association of single nucleotide polymorphism and haplotype of three sites in gene regulation region of protein C(PC) with plasma PC level and susceptibility to pulmonary thromboembolism (PTE) in Shanghai Hah population. Methods A case-control study was adopted. The genotype, allele and haplotype frequency of three polymorphic sites (-1654C/T,-1641A/G and -1476A/T) were determined and analyzed by direct sequencing in 110 patients with PTE and 100 healthy controls. The plasma PC level was detected by enzyme linked immunosorbent assay. group (P ＜ 0.01 or P ＜ 0.05). There was no statistical significance on the family history of thromboembolism and cardiovascular diseases, trauma history, history of oral contraceptives, smoking distribution of PC gene - 1654C/T site between the two groups. T allele frequency was higher in case group, C allele frequency was higher in control group. There was no statistical significance on genotype Haplotype analysis showed that three polymorphism sites of PC gene composed three kinds of haplotype ( - 1654T/- 164 1A/- 1476A, - 1654C/- 164 1A/- 1476A and - 1654C/- 1641G/- 1476T ). There was statistical significance on frequency distribution of TAA and CAA haplotypes between the two groups CAA was lower than that in subjects carried CAA and non-carried TAA, but there was no statistical significance between the two groups. Conclusions PC gene regulatory region polymorphism may be associated with the susceptibility to PTE in Shanghai Han population, but it is further confirmed that the association of PC gene polymorphism with plasma PC level.

Association of protein C gene polymorphism with plasma protein C level and risk of pulmonary thromboembolism in Shanghai Han population

Objective To investigate the association of single nucleotide polymorphism and haplotype of three sites in gene regulation region of protein C(PC) with plasma PC level and susceptibility to pulmonary thromboembolism (PTE) in Shanghai Hah population. Methods A case-control study was adopted. The genotype, allele and haplotype frequency of three polymorphic sites (-1654C/T,-1641A/G and -1476A/T) were determined and analyzed by direct sequencing in 110 patients with PTE and 100 healthy controls. The plasma PC level was detected by enzyme linked immunosorbent assay. group (P ＜ 0.01 or P ＜ 0.05). There was no statistical significance on the family history of thromboembolism and cardiovascular diseases, trauma history, history of oral contraceptives, smoking distribution of PC gene - 1654C/T site between the two groups. T allele frequency was higher in case group, C allele frequency was higher in control group. There was no statistical significance on genotype Haplotype analysis showed that three polymorphism sites of PC gene composed three kinds of haplotype ( - 1654T/- 164 1A/- 1476A, - 1654C/- 164 1A/- 1476A and - 1654C/- 1641G/- 1476T ). There was statistical significance on frequency distribution of TAA and CAA haplotypes between the two groups CAA was lower than that in subjects carried CAA and non-carried TAA, but there was no statistical significance between the two groups. Conclusions PC gene regulatory region polymorphism may be associated with the susceptibility to PTE in Shanghai Han population, but it is further confirmed that the association of PC gene polymorphism with plasma PC level.