白介素6和10基因多态性对动脉粥样硬化长期进展的影响

项目名称： 白介素6和10基因多态性对动脉粥样硬化长期进展的影响

项目编号： No.30872168

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 谢高强

作者单位： 中国医学科学院

项目金额： 34万元

中文摘要： 在"中美心肺流行病学合作研究"北京社区自然人群中选择1700人进行前瞻性分子流行病学研究，小样本（n=40）研究初步证实白介素（IL）-10基因多态性对单核细胞IL-10的表达存在显著影响，IL-6基因多态性对IL-6的表达存在一定的影响，但尚未达到显著性水平。大样本横断面研究证实，IL-6基因3个多态性（rs1800796、rs1524107、rs2066992）以及IL-10基因3个多态性（rs1800872、rs1554286、rs3021094）均与颈动脉斑块的患病危险存在显著相关关系(p<0.05)。大样本前瞻性研究又证实IL-6基因rs1800796多态性、IL-10基因rs1800872和rs1554286多态性对5年后颈动脉斑块新发生率存在显著影响（p<0.05）。基线IL-6浓度显著增加5年后新颈动脉斑块发生危险（p=0.0326），这一作用独立于年龄和性别混杂作用。 上述研究结果提示，以IL-6和10为代表的一系列细胞因子和炎症因子基因及其蛋白表达对中国人群动脉粥样硬化存在显著影响，具有重要的学术研究价值和临床及预防应用价值。

中文关键词： 炎症因子；动脉粥样硬化；白介素6；白介素10；队列研究

英文摘要： We have carried out a prospective genetic epidemiologic study in a community-based natural population (n=1700) in Beijing from the PRC-USA Collaborative Study of Cardiovascular &amp; Cardiopulmonary Epidemiology. We found that 3 SNPs(rs1800872,rs1554286, and rs3021094)of IL-10 gene significantly impact the expression of IL-10 after activated by ox-LDL(p&lt;0.05) in small sample(n=40). The impacts of 3 SNPs （rs1800796,rs1524107,and rs2066992）of IL-6 gene on IL-6 expression were not significant. All 3 SNPs of Il-6 gene and all 3 SNPs of IL-10 gene were significantly associated with risk of carotid plaque in a cross-sectional survey on a large community-based sample(p&lt;0.05). Prospective study in this large sample proved that rs1800796 of IL-6 gene, rs1800872 and rs1554286 of Il-10 gene significantly impact the risk of incidence of new carotid plaque in 5-years following-up(p&lt;0.05). It also proved that baseline IL-6 level significantly increased the risk of new carotid plaque 5 years later， which is independent of confounding effect of age and sex. In summary, the above results suggest that inflammatory factors(represented by IL-6 and 10) genes and their protein expression have important impacts on the incidence of atherosclerosis, then have important values for future academic studies and clinical and preventive applications for Chinese population.

英文关键词： inflammatory factors;atherosclerosis; interleukin-6; interleukin-10;cohort study