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中国天津心肌梗死或脑梗死患者纤溶酶原激活物抑制剂-1 4G/5G基因多态性

Plasminogen activator inhibitor-1 4G/5G gene polymorphism in patients with myocardial or cerebrovascular infarction in Tianjin, China.

作者信息

Zhan Mei, Zhou Yuling, Han Zhongchao

机构信息

State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Science, Tianjin 300020, China.

出版信息

Chin Med J (Engl). 2003 Nov;116(11):1707-10.

Abstract

OBJECTIVE

To investigate the association between the plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene polymorphism and the occurrence of myocardial and cerebrovascular infarctions in individuals from Tianjin, China.

METHODS

The PAI-1 genotype was determined using allele-specific polymerase chain reaction (AS-PCR) in 56 myocardial infarction (MI) patients, 54 cerebrovascular infarction (CI) patients and 83 unrelated healthy controls. All subjects' clinical features and plasma PAI-1 activity levels were determined.

RESULTS

The PAI-1 genotype distribution frequency of the single guanine deletion/insertion 4G/5G polymorphism (located -675 bp upstream from the start of transcription) significantly differed between the patients and healthy controls. In the MI group, the 4G/4G-genotype frequency was increased, but the 4G/5G-genotype is decreased when compared to the control group. In the CI group, both the 4G/4G- and 4G/5G -genotypes occurred at a lower frequency than those in the control group (P < 0.001). The plasma PAI-1 activity level in the MI group was lowered as the presence of the 4G allele decreases. In the CI group, the frequency of 5G/5G was much higher than that of the control group (P < 0.001). The plasma PAI-1 activity level in the CI group was elevated as the presence of the 5G allele increased. Furthermore, positive correlation between triglyceride, glucose levels and PAI-1 activity were found in all three groups (P < 0.001).

CONCLUSIONS

The PAI-1 4G/5G gene polymorphism is associated with a higher risk of MI and CI in individuals in Tianjin, China. The deletion/insertion polymorphism is probably an important hereditary risk factor for heart diseases. Moreover, triglyceride and glucose levels of plasma have functional importance in regulating PAI-1 activity.

摘要

目的

研究中国天津地区人群纤溶酶原激活物抑制剂-1(PAI-1)4G/5G基因多态性与心肌梗死和脑梗死发生之间的关联。

方法

采用等位基因特异性聚合酶链反应(AS-PCR)对56例心肌梗死(MI)患者、54例脑梗死(CI)患者及83例无亲缘关系的健康对照者进行PAI-1基因分型,并测定所有受试者的临床特征及血浆PAI-1活性水平。

结果

患者与健康对照者之间,位于转录起始点上游-675 bp处的单鸟嘌呤缺失/插入4G/5G多态性的PAI-1基因型分布频率存在显著差异。在MI组中,与对照组相比,4G/4G基因型频率升高,而4G/5G基因型频率降低。在CI组中,4G/4G和4G/5G基因型出现的频率均低于对照组(P<0.001)。MI组血浆PAI-1活性水平随着4G等位基因的存在减少而降低。在CI组中,5G/5G的频率远高于对照组(P<0.001)。CI组血浆PAI-1活性水平随着5G等位基因的存在增加而升高。此外,在所有三组中均发现甘油三酯、血糖水平与PAI-1活性之间呈正相关(P<0.001)。

结论

PAI-1 4G/5G基因多态性与中国天津地区人群发生MI和CI的较高风险相关。该缺失/插入多态性可能是心脏病的一个重要遗传危险因素。此外,血浆甘油三酯和血糖水平在调节PAI-1活性方面具有重要作用。

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