Zhan Mei, Zhou Yuling, Han Zhongchao
State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Science, Tianjin 300020, China.
Chin Med J (Engl). 2003 Nov;116(11):1707-10.
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.
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.
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).
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.
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。
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。
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)。
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。