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[冠心病患者血管性血友病因子基因A1381T多态性分析]

[Analysis of vWF gene A1381T polymorphism in patients with coronary heart disease].

作者信息

Yuan Zhong-Hai, Hou Yi-Ju, Li Yan, Zhang Hui, Li Zhong-Yan, Li Xin, Yu Dong-Hui

机构信息

Section of Blood Examination, Department of Medical Laboratory Examination, Jilin Medical and Pharmaceutical College, Jilin 132013, Jilin Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2011 Jun;19(3):775-80.

Abstract

This study was purposed to investigate the vWF gene A1381T polymorphism in patients with coronary heart disease (CHD). A case-control study was designed, including 104 continuously hospitalized patients with CHD, aging from 40 to 75 years (average 59) and 96 persons underwent physical examination in outpatient department as controls, aging from 39 to 70 years (average 56). The plasma vWF: Ag level of CHD patients and control persons was detected by ILISA. vWF gene A1381T polymorphism was analyzed by the polymerase chain reaction-restriction fragment length polymorphism and sequencing when it is necessary. The data were grouped by gender, blood group and/or genotype in CHD group and control groups. The difference of plasma vWF level between male and female was analyzed by independent sample t test; one way ANOVA was used to analyze the difference of vWF level between different blood group genotypes, while the factorial design ANOVA was used to test the difference of vWF level in plasma between A1381T genotype and/or ABO blood groups. χ(2) Crosstabs were used to test the CHD susceptibility. The results showed that the frequencies of GG genotype (wild type) of vWF gene A1381T polymorphism were 62.5% in CHD group and 67.7% in control group, and the frequencies of AG genotype (heterozygous variant) were 37.5% in CHD group and 32.3% in control group. χ(2) Crosstabs showed no significant correlation between vWF gene A1381T polymorphism (AG) and CHD (OR = 1.258, 95% CI = 0.702 - 2.255, χ(2) = 0.595, p = 0.440). The plasma vWF level in CHD group was statistically very higher than that in control group (p < 0.001), even though the relationship of vWF A1381T polymorphism (rs216311) and susceptibility of CHD in CHD group was not found. The plasma vWF level of AG or GG genotype was higher in CHD group than in control group (p < 0.001). The plasma vWF level of AG genotype was higher than that of GG in CHD group (p < 0.05), but not in control group. The plasma vWF of O blood group was lower than that of A, B and AB blood groups (p < 0.05), while among A, B, AB blood groups, the vWF level was not different (p > 0.05). Among O, A, B, AB blood groups in CHD group, vWF level was not different (p > 0.05). Although the two-way analysis of variance ANOVA showed no interaction of A1381T genotype and ABO blood groups on plasma vWF level, the plasma vWF level in AG mutant of vWF A1381T gene polymorphism with O blood group was higher than that of GG mutant (p = 0.023) in CHD group, not different in other blood groups. It is concluded that there is no association between vWF gene A1381T polymorphism and CHD susceptibility. The plasma vWF level in CHD group interrelated with ABO blood group and A1381T polymorphism, in which the plasma vWF level in AG genotype increase mostly. Plasma vWF level in vWF gene A1381T polymorphism with AG mutant was significantly much higher than GG mutant in CHD. This change may be beneficial to further study the effect of A1381T polymorphism on vWF gene expression and activity.

摘要

本研究旨在探讨冠心病(CHD)患者血管性血友病因子(vWF)基因A1381T多态性。设计了一项病例对照研究,纳入104例年龄40至75岁(平均59岁)的持续住院冠心病患者,并选取96例年龄39至70岁(平均56岁)在门诊接受体检的人员作为对照。采用酶联免疫吸附测定法(ILISA)检测冠心病患者和对照者的血浆vWF:Ag水平。必要时,通过聚合酶链反应-限制性片段长度多态性和测序分析vWF基因A1381T多态性。数据按冠心病组和对照组的性别、血型和/或基因型分组。采用独立样本t检验分析男性和女性血浆vWF水平的差异;采用单因素方差分析分析不同血型基因型之间vWF水平的差异,而采用析因设计方差分析检验A1381T基因型和/或ABO血型之间血浆vWF水平的差异。采用χ(2)交叉表检验冠心病易感性。结果显示,vWF基因A1381T多态性的GG基因型(野生型)频率在冠心病组为62.5%,在对照组为67.7%,AG基因型(杂合变异型)频率在冠心病组为37.5%,在对照组为32.3%。χ(2)交叉表显示vWF基因A1381T多态性(AG)与冠心病之间无显著相关性(OR = 1.258,95%CI = 0.702 - 2.255,χ(2) = 0.595,p = 0.440)。冠心病组血浆vWF水平在统计学上显著高于对照组(p < 0.001),尽管未发现冠心病组中vWF A1381T多态性(rs216311)与冠心病易感性之间的关系。冠心病组中AG或GG基因型的血浆vWF水平高于对照组(p < 0.001)。冠心病组中AG基因型的血浆vWF水平高于GG基因型(p < 0.05),但在对照组中无此差异。O血型的血浆vWF低于A、B和AB血型(p < 0.05),而在A、B、AB血型之间,vWF水平无差异(p > 0.05)。冠心病组中O、A、B、AB血型之间,vWF水平无差异(p > 0.05)。尽管双向方差分析显示A1381T基因型和ABO血型对血浆vWF水平无交互作用,但冠心病组中vWF A1381T基因多态性AG突变型且为O血型者的血浆vWF水平高于GG突变型(p = 0.023),在其他血型中无差异。结论:vWF基因A1381T多态性与冠心病易感性无关。冠心病组血浆vWF水平与ABO血型和A1381T多态性相关,其中AG基因型的血浆vWF水平升高最为明显。冠心病中vWF基因A1381T多态性AG突变型的血浆vWF水平显著高于GG突变型。这一变化可能有助于进一步研究A1381T多态性对vWF基因表达和活性的影响。

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