CD40-1C/T基因多态性与大动脉粥样硬化性卒中的相关性
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摘要
目的探讨CD40基因启动子区域-1位C/T(CD40一1C/T)基因多态性与颈动脉粥样硬化斑块及大动脉粥样硬化性卒中的相关性,发现缺血性脑卒中的易感基因。
方法根据入选条件选取急性大动脉粥样硬化性卒中患者170例作为病例组,据颈动脉超声检查结果将病例组分为不稳定斑块组(51例)、稳定斑块组(60例)、无斑块组(59例)；选取无卒中病史体检者作为对照组(61例)；采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测所有研究对象CD40一1C/T基因多态性。
结果(1)病例组C等位基因频率(52.9%)、CC基因型频率(30.6%)明显高于对照组(38.5%,16.4%)差异有统计学意义(X2=7.466,P=0.006；X2=4.606,P=0.032)；而T等位基因频率(47.1%)、TT基因型频率(24.7%)明显低于对照组(61.5%,39.3%),差异有统计学意义(X2=7.466,P=0.006；X2=4.714,P=0.030)；(2)病例组两两比较结果示不稳定斑块组C等位基因频率(75.5%)、CC基因型频率(52.9%)明显高于稳定斑块组(53.3%,30%)且均高于无斑块组(33.1%,11.9%),差异有统计学意义(稳定斑块组与无斑块组比较：X2=9.970,P=0.002；不稳定斑块组与稳定斑块组比较：X2=11.680,P=0.001;不稳定斑块组与无斑块组比较：X2=39.532,P=0.000。稳定斑块组与无斑块组比较：X2=5.896,P=0.015;不稳定斑块组与稳定斑块组比较：X2=6.019,P=0.014；不稳定斑块组与无斑块组比较：X2=21.613,P=0.000。),而T等位基因频率(24.5%)、TT基因型频率(2%)明显低于稳定斑块组(46.7%,23.3%)且均低于无斑块组(66.9%,45.8%),差异有统计学意义(稳定斑块组与无斑块组比较：X2=9.970,P=0.002；不稳定斑块组与稳定斑块组比较：X2=11.680,P=0.001；不稳定斑块组与无斑块组比较：X2=39.532,P=0.000。稳定斑块组与无斑块组比较：X2=6.627,P=0.010；不稳定斑块组与稳定斑块组比较：X2=10.774,P=0.001；不稳定斑块组与无斑块组比较：X2=27.659,P=0.000。)；(3)C等位基因的携带者大动脉粥样硬化性卒中的患病风险是对照组的1.795倍(OR=1.795,95%CI1.177-2.738)；(4)C等位基因的携带者颈动脉稳定斑块形成的风险是无斑块组的2.315倍(稳定斑块组与无斑块组比较OR=2.315,95%CI1.369-3.914)；C等位基因的携带者颈动脉不稳定性斑块形成的风险是稳定斑块组的2.695倍(不稳定斑块组与稳定斑块组比较OR=2.695,95%CI1.514-4.796),是无斑块组的6.239倍(不稳定斑块组与无斑块组比较OR=6.239,95%CI3.451-11.280)。
结论CD40-1C/T基因多态性与颈动脉粥样硬化斑块形成及不稳定性、缺血性卒中相关,C等位基因增加颈动脉粥样硬化斑块的形成与不稳定性进而导致缺血性卒中的发生,C等位基因可能为缺血性卒中的易感基因。
Objective To investigate whether CD40gene (-1C/T) single nucleotide polymorphism(SNP) is associated with the stability of carotid artery plaque, while analyse the association CD40gene (-1C/T) single nucleotide polymorphism(SNP) and occurrence of ischemic cerebrovascular disease.
.Methods:170patients with acute ischemic cerebrovascular disease were selected as cerebral infarction group,all subjects were detected the plaque echogenicity and morphology were evaluated bilaterally by carotid ultrasonography. According to the results, all patients in cerebral infarction group were divided into three subgroups, including unstable plaque group(51cases), stable plaque group(60cases) and non-plaque group(59cases)and61persons without cerebrovascular disease were selected as control group. The gene polymorphism was measured by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFL P).
Results:①The frequency of the C allele (52.9%) and the CC genotype (30.6%) in cerebral infarction group was significantly higher than that of the controls (38.5%,16.4%).(X2=7.466, P=0.006; X2=4.606, P=0.032). The frequency of the T allele (47.1%) and the TT genotype (24.7%) in cerebral infarction group was significantly lower than that of the controls (61.5%,39.3%).(X2=7.466, P=0.006; X2=4.714, P=0.030).②The frequency of the C allele (75.5%) and the CC genotype (52.9%) in unstable plaque group were significantly higher than that in stable plaque group (53.3%,30%), and were both significantly higher than that in non-plaque group63.1%11.9%).(stable plaque group vs non-plaque group:X2=9.970, P=0.002; unstable plaque group vs stable plaque group:X2=11.680, P=0.001; unstable plaque group vs non-plaque group:X2=39.532, P=0.000. stable plaque group vs non-plaque group:X2=5.896, P=0.015; unstable plaque group vs stable plaque group:X2=6.019, P=0.014; unstable plaque group vs non-plaque group:X2=21.613, P=0.000.) The frequency of the T allele (24.5%) and the TT genotype (2%) in unstable plaque group were significantly lower than that in stable plaque group (46.7%,23.3%), and were both significantly lower than that in non-plaque group (66.9%,45.8%).(stable plaque group vs non-plaque group:X2=9.970, P=0.002; unstable plaque group vs stable plaque group:X2=11.680, P=0.001; unstable plaque group vs non-plaque group:X2=39.532, P=0.000. stable plaque group vs non-plaque group:X2=6.627, P=0.010; unstable plaque group vs stable plaque group:X2=10.774, P=0.001; unstable plaque group vs non-plaque group:X2=27.659, P=0.000.)③The C allele increased the risk of cerebral infarction as the cerebral infarction group compared with the the controls.(OR=1.795,95%CI1.177-2.738).④The C allele increased the risk of the formation of atherosclerotic plaque as the stable plaque group compared with the controls.(OR=2.315,95%CI1.369-3.914), the C allele increased the risk of the formation of unstable plaque as the unstable plaque group compared with the stable plaque group.(OR=2.695,95%CI1.514-4.796), the C allele increased the risk of the formation of unstable plaque as the unstable plaque group compared with non-plaque group.(OR=6.239,95%CI3.451-11.280)
Conclusions:CD40-1C/T polymorphism is associated with the development of the formation of carotid atherosclerosis plaque, the formation of unstable stable carotid atherosclerosis plaque,and ischemic cerebrovascular disease.The C allele frequency maybe participate the development of the formation of carotid atherosclerosis plaque and stable carotid atherosclerosis plaque to unstable by promoting plaque rupture, which can lead to occurrence and recurrence of ischemic cerebrovascular disease.
方法根据入选条件选取急性大动脉粥样硬化性卒中患者170例作为病例组,据颈动脉超声检查结果将病例组分为不稳定斑块组(51例)、稳定斑块组(60例)、无斑块组(59例)；选取无卒中病史体检者作为对照组(61例)；采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测所有研究对象CD40一1C/T基因多态性。
结果(1)病例组C等位基因频率(52.9%)、CC基因型频率(30.6%)明显高于对照组(38.5%,16.4%)差异有统计学意义(X2=7.466,P=0.006；X2=4.606,P=0.032)；而T等位基因频率(47.1%)、TT基因型频率(24.7%)明显低于对照组(61.5%,39.3%),差异有统计学意义(X2=7.466,P=0.006；X2=4.714,P=0.030)；(2)病例组两两比较结果示不稳定斑块组C等位基因频率(75.5%)、CC基因型频率(52.9%)明显高于稳定斑块组(53.3%,30%)且均高于无斑块组(33.1%,11.9%),差异有统计学意义(稳定斑块组与无斑块组比较：X2=9.970,P=0.002；不稳定斑块组与稳定斑块组比较：X2=11.680,P=0.001;不稳定斑块组与无斑块组比较：X2=39.532,P=0.000。稳定斑块组与无斑块组比较：X2=5.896,P=0.015;不稳定斑块组与稳定斑块组比较：X2=6.019,P=0.014；不稳定斑块组与无斑块组比较：X2=21.613,P=0.000。),而T等位基因频率(24.5%)、TT基因型频率(2%)明显低于稳定斑块组(46.7%,23.3%)且均低于无斑块组(66.9%,45.8%),差异有统计学意义(稳定斑块组与无斑块组比较：X2=9.970,P=0.002；不稳定斑块组与稳定斑块组比较：X2=11.680,P=0.001；不稳定斑块组与无斑块组比较：X2=39.532,P=0.000。稳定斑块组与无斑块组比较：X2=6.627,P=0.010；不稳定斑块组与稳定斑块组比较：X2=10.774,P=0.001；不稳定斑块组与无斑块组比较：X2=27.659,P=0.000。)；(3)C等位基因的携带者大动脉粥样硬化性卒中的患病风险是对照组的1.795倍(OR=1.795,95%CI1.177-2.738)；(4)C等位基因的携带者颈动脉稳定斑块形成的风险是无斑块组的2.315倍(稳定斑块组与无斑块组比较OR=2.315,95%CI1.369-3.914)；C等位基因的携带者颈动脉不稳定性斑块形成的风险是稳定斑块组的2.695倍(不稳定斑块组与稳定斑块组比较OR=2.695,95%CI1.514-4.796),是无斑块组的6.239倍(不稳定斑块组与无斑块组比较OR=6.239,95%CI3.451-11.280)。
结论CD40-1C/T基因多态性与颈动脉粥样硬化斑块形成及不稳定性、缺血性卒中相关,C等位基因增加颈动脉粥样硬化斑块的形成与不稳定性进而导致缺血性卒中的发生,C等位基因可能为缺血性卒中的易感基因。
Objective To investigate whether CD40gene (-1C/T) single nucleotide polymorphism(SNP) is associated with the stability of carotid artery plaque, while analyse the association CD40gene (-1C/T) single nucleotide polymorphism(SNP) and occurrence of ischemic cerebrovascular disease.
.Methods:170patients with acute ischemic cerebrovascular disease were selected as cerebral infarction group,all subjects were detected the plaque echogenicity and morphology were evaluated bilaterally by carotid ultrasonography. According to the results, all patients in cerebral infarction group were divided into three subgroups, including unstable plaque group(51cases), stable plaque group(60cases) and non-plaque group(59cases)and61persons without cerebrovascular disease were selected as control group. The gene polymorphism was measured by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFL P).
Results:①The frequency of the C allele (52.9%) and the CC genotype (30.6%) in cerebral infarction group was significantly higher than that of the controls (38.5%,16.4%).(X2=7.466, P=0.006; X2=4.606, P=0.032). The frequency of the T allele (47.1%) and the TT genotype (24.7%) in cerebral infarction group was significantly lower than that of the controls (61.5%,39.3%).(X2=7.466, P=0.006; X2=4.714, P=0.030).②The frequency of the C allele (75.5%) and the CC genotype (52.9%) in unstable plaque group were significantly higher than that in stable plaque group (53.3%,30%), and were both significantly higher than that in non-plaque group63.1%11.9%).(stable plaque group vs non-plaque group:X2=9.970, P=0.002; unstable plaque group vs stable plaque group:X2=11.680, P=0.001; unstable plaque group vs non-plaque group:X2=39.532, P=0.000. stable plaque group vs non-plaque group:X2=5.896, P=0.015; unstable plaque group vs stable plaque group:X2=6.019, P=0.014; unstable plaque group vs non-plaque group:X2=21.613, P=0.000.) The frequency of the T allele (24.5%) and the TT genotype (2%) in unstable plaque group were significantly lower than that in stable plaque group (46.7%,23.3%), and were both significantly lower than that in non-plaque group (66.9%,45.8%).(stable plaque group vs non-plaque group:X2=9.970, P=0.002; unstable plaque group vs stable plaque group:X2=11.680, P=0.001; unstable plaque group vs non-plaque group:X2=39.532, P=0.000. stable plaque group vs non-plaque group:X2=6.627, P=0.010; unstable plaque group vs stable plaque group:X2=10.774, P=0.001; unstable plaque group vs non-plaque group:X2=27.659, P=0.000.)③The C allele increased the risk of cerebral infarction as the cerebral infarction group compared with the the controls.(OR=1.795,95%CI1.177-2.738).④The C allele increased the risk of the formation of atherosclerotic plaque as the stable plaque group compared with the controls.(OR=2.315,95%CI1.369-3.914), the C allele increased the risk of the formation of unstable plaque as the unstable plaque group compared with the stable plaque group.(OR=2.695,95%CI1.514-4.796), the C allele increased the risk of the formation of unstable plaque as the unstable plaque group compared with non-plaque group.(OR=6.239,95%CI3.451-11.280)
Conclusions:CD40-1C/T polymorphism is associated with the development of the formation of carotid atherosclerosis plaque, the formation of unstable stable carotid atherosclerosis plaque,and ischemic cerebrovascular disease.The C allele frequency maybe participate the development of the formation of carotid atherosclerosis plaque and stable carotid atherosclerosis plaque to unstable by promoting plaque rupture, which can lead to occurrence and recurrence of ischemic cerebrovascular disease.
引文
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