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动脉粥样硬化是一种炎症性疾病,个体及环境因素等综合作用导致其发生和发展。动脉粥样硬化的细胞因子如白细胞介素(IL)-1家族参与了动脉粥样硬化的形成过程[1-3]。IL-1RN和IL-1β基因多态性被认为是动脉粥样硬化斑块形成的影响因素之一。研究[4-5]显示,IL-1家族数目可变串联重复序列(variable number of tandem repeats,VNTR)和单核苷酸多态性(single nucleotide polymorphisms,SNPs)基因多态性与冠心病密切相关。同时,研究[6]发现,幽门螺旋杆菌(HP)感染不仅与消化性溃疡相关,也与动脉粥样硬化相关。我们以踝臂指数(ABI)作为动脉粥样硬化的标志参数,探讨动脉粥样硬化的发生、发展过程中IL-1β-511和IL-1RN VNTR基因多态性与HP感染是否存在协同作用。现作报道。
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HP阳性组年龄、男性比例、体质量、体质量指数(BMI)均大于阴性组(P < 0.05~P < 0.01),高密度脂蛋白(HDL)和总胆固醇(TC)水平均低于阴性组(P < 0.05和P < 0.01),2组身高、高血压、吸烟行为、低密度脂蛋白(LDL)差异均无统计学意义(P > 0.05)(见表 1)。
分组 n 年龄/岁 男 女 身高/cm 体质量/kg BMI/
(kg/m2)高血压 吸烟 HDL/
(mg/dL)LDL/
(mg/dL)TC/(mg/dL) 是 否 HP阴性组 97 50.8±12.1 52 45 168.3±9.8 65.5±10.4 25.1±4.0 39 28 69 50.8±10.1 146.0±29.8 211.2±51.3 HP阳性组 129 54.8±14.6 93 36 169.2±7.0 70.8±9.0 29.1±5.1 65 40 89 47.3±11.4 138.2±40.3 192.0±42.6 t — 2.19 8.23* 0.77 4.1 6.61 2.31* 1.03* 2.4 1.67 2.99 P — < 0.05 < 0.01 > 0.05 < 0.01 < 0.01 > 0.05 > 0.05 < 0.05 > 0.05 < 0.01 *示χ2值 表 1 HP阴性和阳性受试者基本情况比较(x ±s)
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HP阴性受试者ABI处于正常值范围的比例高于HP阳性、CagA阳性、VagA阳性组(P < 0.01),HP阳性、CagA阳性、VagA阳性3组ABI处于正常值范围的比例差异无统计学意义(P > 0.05)(见表 3)。
分组 n ABI χ2 P 正常 轻度低 较低 HP阳性组 129 90(69.8) 35(27.1) 4(3.1) 16.15 < 0.01 HP阴性组
CagA阳性组97
11987(89.7)
84(71.4)10(10.3)
31(26.1)0(0.0)
4(3.3)VagA阳性组 112 74(66.1) 34(30.3) 4(3.6) 表 2 HP阳性和阴性受试者的ABI分布情况[n;百分率(%)]
基因型 n ABI χ2 P 正常 轻度低 较低 CC 37(15.6) 29(78.4) 7(18.9) 1(2.7) 3.05 > 0.05 CT 147(62.0) 112(76.2) 31(21.8) 3(2.0) TT 53(22.4) 46(86.8) 7(13.2) 0(0.0) 表 3 IL-1β-511基因多态性与ABI分布[n;构成比(%)]
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IL-1β-511基因型分布频率分别为TT 22.4%、CC 15.6%和CT 62.0%,各基因型ABI分布情况差异无统计学意义(P > 0.05)(见表 3)。IL1-RN VNTR等位基因频率分布情况为等位基因频率重复4次(IL-1RN*1)85.5%、2次(IL-1RN*2)29.2%,少数为IL-1RN*3,符合Hardy-Weinberg平衡分布,各基因型ABI分布情况差异无统计学意义(P > 0.05)(见表 4)。
IL-1RN
等位基因n ABI χ2 P 正常 轻度低 较低 IL-1RN*1 194(85.5) 155(79.9) 36(18.6) 3(1.5) 2.83 > 0.05 IL-1RN*2 21 (9.2) 14(66.7) 6(28.4) 1(4.8) IL-1RN*3 13(5.7) 10(76.9) 3(23.0) 0(0.0) 表 4 IL-1 RN VNTR基因多态性与ABI分布[n;构成比(%)]
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校正年龄、性别、吸烟行为和BMI、血脂、IL-1基因影响后,多因素logistic回归分析结果显示,HP感染与ABI间无明显相关性(P>0.05),CagA阳性是低ABI值的危险因素(P < 0.01)(见表 5)。
ABI 变量 B SE Wald Exp(B) 95%CI P < 0.9 HP阳性 -0.636 1.210 0.276 0.899 0.838~1.535 > 0.05 < 0.9 CagA阳性 7.103 1.083 2.325 2.704 1.562~3.981 < 0.01 < 0.9 VacA阳性 -8.713 1.432 4.21 1.761 0.912~3.328 > 0.05 表 5 低ABI、IL-1基因多态性与HP感染的相关性分析
白细胞介素-1基因多态性及幽门螺旋杆菌感染与健康中年人群动脉粥样硬化程度的相关性
The relationship between the interleukin-1 gene polymorphism and Helicobacter pylori infection, and atherosclerosis in healthy middle-aged population
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摘要:
目的探讨白细胞介素(IL)-1基因IL-1β-511、IL-1 RN VNTR位点多态性在幽门螺旋杆菌(HP)感染加重健康中年人群动脉粥样硬化程度中的作用。 方法以聚合酶链反应限制性片段长度多态性分析法检测227名健康中年人IL-1β-511、IL-1 RN VNTR位点多态性,ELISA法检测HP IgG及CagA、VacA抗体,通过臂踝指数(ABI)评估受试者动脉粥样硬化程度。 结果IL-1β-511多态性分别为CT(64.8%)、TT(22.3%),IL-1RN VNTR片段倍数多态性分别为IL-1RN*1(68.7%)、2倍重复(IL-1RN*2)(29.2%)。不同IL-1基因多态性受试者的ABI差异无统计学意义(P>0.05)。HP阳性受试者ABI明显低于阴性者(P < 0.01)。校正年龄、性别、高血压、糖尿病、抽烟状态、BMI、高脂血症及IL-1基因多态性后,ABI在HP阴性组及阳性组间差异无统计学意义(P>0.05),HP CagA抗体阳性是低ABI的危险因素(P < 0.01)。 结论HP感染,尤其是CagA抗体阳性HP感染,可能是中国南方汉族中年人群动脉粥样硬化的一个危险因素,与2种IL-1基因位点多态性无明显相关性。 -
关键词:
- 动脉粥样硬化 /
- 白细胞介素-1β-511 /
- 白细胞介素-1 RN VNTR /
- 幽门螺旋杆菌 /
- 踝臂指数
Abstract:ObjectiveTo investigate the effects of the gene polymorphism of IL-1-511 or IL-1RN VNTR on atherosclerosis in Helicobacter pylori (HP) infection aggravation healthy middle-aged people. MethodsThe genotypes loci polymorphism of IL-1 511 or IL-1RN VNTR in 227 healthy middle-aged people were determined using polymerase chain reaction(PCR)-restriction digestion analysis.The HP IgG, and CagA and VacA antibody were detected using ELISA, and the degree of atherosclerosis was assessed using the ankle-brachial index(ABI). ResultsThe main polymorphism of IL-1β-511 were CT(64.8%) and TT(22.3%), respectively.The allele frequency of four-repeat(IL-1RN*1) was 68.7%, and two repeat(IL-1RN*2) alleles was 29.2% in IL-1RN VNTR.The difference of ABI in subjects with different Il-1 gene polymorphisms was not statistically significant(P>0.05).The ABI in positive HP subjects was significantly lower than that in negative HP subjects(P < 0.01).After adjusting the age, sex, hypertension, diabetes, smoking status, BMI, triglyceride and interleukin-1 Gene polymorphism, the difference of the ABI between positive and negative HP subjects was not statistically significant(P>0.05), and the positive HP CagA antibody was a low risk factor of ABI(P < 0.01). ConclusionsThe HP infection, especially CagA antibody-positive HP infection, may be a risk factor of atherosclerosis in the middle-aged Han population in southern China, and there is no significant correlation between it and polymorphisms of two IL-1 gene sites. -
Key words:
- atherosclerosis /
- interleukin 1 IL-1β-511 /
- IL-1 RN VNTR /
- Helicobacter pylori /
- ankle-brachial index
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表 1 HP阴性和阳性受试者基本情况比较(x ±s)
分组 n 年龄/岁 男 女 身高/cm 体质量/kg BMI/
(kg/m2)高血压 吸烟 HDL/
(mg/dL)LDL/
(mg/dL)TC/(mg/dL) 是 否 HP阴性组 97 50.8±12.1 52 45 168.3±9.8 65.5±10.4 25.1±4.0 39 28 69 50.8±10.1 146.0±29.8 211.2±51.3 HP阳性组 129 54.8±14.6 93 36 169.2±7.0 70.8±9.0 29.1±5.1 65 40 89 47.3±11.4 138.2±40.3 192.0±42.6 t — 2.19 8.23* 0.77 4.1 6.61 2.31* 1.03* 2.4 1.67 2.99 P — < 0.05 < 0.01 > 0.05 < 0.01 < 0.01 > 0.05 > 0.05 < 0.05 > 0.05 < 0.01 *示χ2值 表 2 HP阳性和阴性受试者的ABI分布情况[n;百分率(%)]
分组 n ABI χ2 P 正常 轻度低 较低 HP阳性组 129 90(69.8) 35(27.1) 4(3.1) 16.15 < 0.01 HP阴性组
CagA阳性组97
11987(89.7)
84(71.4)10(10.3)
31(26.1)0(0.0)
4(3.3)VagA阳性组 112 74(66.1) 34(30.3) 4(3.6) 表 3 IL-1β-511基因多态性与ABI分布[n;构成比(%)]
基因型 n ABI χ2 P 正常 轻度低 较低 CC 37(15.6) 29(78.4) 7(18.9) 1(2.7) 3.05 > 0.05 CT 147(62.0) 112(76.2) 31(21.8) 3(2.0) TT 53(22.4) 46(86.8) 7(13.2) 0(0.0) 表 4 IL-1 RN VNTR基因多态性与ABI分布[n;构成比(%)]
IL-1RN
等位基因n ABI χ2 P 正常 轻度低 较低 IL-1RN*1 194(85.5) 155(79.9) 36(18.6) 3(1.5) 2.83 > 0.05 IL-1RN*2 21 (9.2) 14(66.7) 6(28.4) 1(4.8) IL-1RN*3 13(5.7) 10(76.9) 3(23.0) 0(0.0) 表 5 低ABI、IL-1基因多态性与HP感染的相关性分析
ABI 变量 B SE Wald Exp(B) 95%CI P < 0.9 HP阳性 -0.636 1.210 0.276 0.899 0.838~1.535 > 0.05 < 0.9 CagA阳性 7.103 1.083 2.325 2.704 1.562~3.981 < 0.01 < 0.9 VacA阳性 -8.713 1.432 4.21 1.761 0.912~3.328 > 0.05 -
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