老年2型糖尿病患者子女纤溶酶原激活物抑制物1基因的多态性

Polymorphism of plasminogen activator inhibitor-1 gene in the children of elderly patients with type 2 diabetes mellitus

目的:检测老年2型糖尿病患者的子女血浆纤溶酶原激活物抑制物1基因型,并分析其与血浆纤溶酶原激活物抑制物1活性、血脂、血糖、体质量指数、腰臀比、胰岛素抵抗之间关系。方法:选择河北省人民医院2002-01/12健康查体者54人作为对照组,男26人,女28人。纳入标准:空腹血糖均低于6.0mmol/L,餐后2h血糖低于7.8mmol/L;无糖尿病、高血压、冠心病家族史。随机抽取同期就诊的2型糖尿病患者的子女92人作为子女组,男44人,女48人。纳入标准:其父母双方或一方为2型糖尿病患者;空腹血糖均低于6.0mmol/L,餐后2h血糖低于7.8mmol/L;两组人员均知情同意。两组人员血浆纤溶酶原激活物抑制物1基因型采用聚合酶链反应检测;血浆纤溶酶原激活物抑制物1活性发色底物法检测。进行两组间及基因型间和等位基因频率的差异性比较。并做各代谢参数与血浆纤溶酶原激活物抑制物1活性的逐步多元直线回归分析。结果:①两组纤溶酶原激活物抑制物1基因基因型和等位基因分布比较:子女组与对照组相比4G/4G+4G/5G基因型频率和4G等位基因频率呈增高趋势,但差异无显著性意义(P>0.05)。②两组不同基因型间血浆纤溶酶原激活物抑制物1活性的比较:对照组和子女组含4G等位基因显著高于不含4G等位基因(0.72±0.21比0.43±0.30,0.95±0.24比0.63±0.22,P<0.05)。③各代谢参数与血浆纤溶酶原激活物抑制物1活性的逐步多元直线回归分析结果:子女组,纤溶酶原激活物抑制物1活性与胰岛素抵抗指数自然对数、三酰甘油和基因型明显相关(r=0.30,P=0.003;r=0.46,P=0.001;r=0.44,P=0.001);正常对照组,纤溶酶原激活物抑制物1活性只与基因型相关(r=0.48,P=0.03)。结论:①老年2型糖尿病患者的子女血浆纤溶酶原激活物抑制物14G等位基因的携带者较多。②携带4G等位基因的人群血浆纤溶酶原激活物抑制物1活性升高。③血浆纤溶酶原激活物抑制物14G等位基因存在可能对2型糖尿病患者及后代血浆纤溶酶原激活物抑制物1活性升高起一定作用。④逐步多元直线回归分析表明,2型糖尿病患者子女胰岛素抵抗以及相关变量等环境因素和4G等位基因这一遗传因素共同影响纤溶酶原激活物抑制物1活性。

AIM: To detect the genotype of plasminogen activator inhibitor-1 gene in the children of elderly patients with type 2 diabetes mellitus, and analyze its correlations with the activity of plasminogen activator inhibitor-1, blood lipid, blood glucose, body mass index, waist-to-hip ratio and insulin resistance. METHODS: Fifty-four healthy physical examinees (26 males and 28 females) in Hebei Provincial People's Hospital from January to December 2002 were selected as controls; inclusion criteria: fasting blood glucose was lower than 6.0 mmol/L, 2-hour postprandial blood glucose was lower than 7.8 mmol/L, without family history of diabetes mellitus, hypertension and coronary heart disease. Ninety-two children (44 males and 48 females) of the type 2 diabetic patients were selected as children group; including 44 males and 48 females; inclusion criteria: at least one of the parents had type 2 diabetes mellitus, fasting blood glucose was lower than 6.0 mmol/L, 2-hour postprandial blood glucose was lower than 7.8 mmol/L. All the subjects in both groups participated in the study voluntarily. The genotype of plasminogen activator inhibitor-1 gene was detected with polymerase chain reaction, the activity of plasminogen activator inhibitor-1 gene was detected with the method of chromogenic substrate. The differences of genotype and allele frequency were compared between the two groups. The correlations of the metabolic indexes with the activity of plasminogen activator inhibitor-1 gene were analyzed with the multiple stepwise linear regression analysis. RESULTS: ① Comparison of the genotype and allele distribution of plasminogen activator inhibitor-1 between the two groups: Compared with the control group, the genotypic frequencies of 4G/4G+4G/5G and the frequency of 4G allele in the children group showed an increasing tendency, but there was insignificant difference (P > 0.05). ② Comparison of the activity of plasminogen activator inhibitor-1 between different genotypes in the two groups: It was significantly higher in the subjects with 4G allele than those without 4G allele in the control group and children group (0.72 ±0.21 vs 0.43±0.30; 0.95±0.24 vs 0.63±0.22, P < 0.05). ③ The results of the multiple stepwise linear regression analysis between the metabolic indexes and the activity of plasminogen activator inhibitor-1: In the children group, the activity of plasminogen activator inhibitor-1 was obviously correlated with the natural logarithm of insulin resistance, triglyceride and the genotype (r=0.30, P=0.003; r=0.46, P=0.001; r=0.44, P=0.001). In the normal control group, the activity of plasminogen activator inhibitor-1 was only correlated with its genotype (r=0.48, P=0.03). CONCLUSION: ① There are more carriers of 4G allele of plasminogen activator inhibitor-1 in the children of elderly patients with type 2 diabetes mellitus. ② The activity of plasminogen activator inhibitor-1 is increased in the carriers of 4G allele. ③ The existence of 4G allele of plasminogen activator inhibitor-1 may be involved in the increase of the activity of plasminogen activator inhibitor-1 in the patients with type 2 diabetes mellitus and their children. ④ The multiple stepwise linear regression analysis indicates that the insulin resistance, the environmental factors of related variables and the genetic factor of 4G allele together affect the activity of plasminogen activator inhibitor-1 in the children of patients with type 2 diabetes mellitus.