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白细胞介素 10 启动子区域多态性与动脉粥样硬化的早期标志物:芬兰年轻人心血管风险研究。

Polymorphism in the IL10 promoter region and early markers of atherosclerosis: the Cardiovascular Risk in Young Finns Study.

机构信息

The Medical School at the University of Tampere, Finland.

出版信息

Atherosclerosis. 2010 Jan;208(1):190-6. doi: 10.1016/j.atherosclerosis.2009.06.032. Epub 2009 Jul 8.

DOI:10.1016/j.atherosclerosis.2009.06.032
PMID:19700159
Abstract

OBJECTIVE

Inflammatory factors modify the risk of coronary heart disease. Pleiotropic cytokine interleukin-10 (IL-10) has been suggested as modifying risk for atherosclerosis. Promoter region genetic polymorphism of IL-10 gene (IL10) is known to be associated with the variation of IL-10 production. We investigated whether single-base exchange polymorphisms -1082 G>A (rs1800896), -819 C>T (rs1800871) and -592 C>A (rs1800872) at IL10 gene are associated with risk factors and early markers of atherosclerosis in young subjects.

METHODS AND RESULTS

As a part of the Cardiovascular Risk in Young Finns Study, we determined carotid artery compliance (CAC), stiffness index (SI) and Young's elastic modulus (YEM), intima media thickness (IMT), IL10 genotype and atherosclerosis risk parameters for 2260 subjects aged 24-39 years. In male subjects CAC was lower in carriers of IL-10 high- to intermediate-producer haplotype -1082 G; -819 C; -592 C (GCC+, 1.96+/-0.67) than in noncarriers (GCC-, 2.10+/-0.62, %/10 mmHg, mean+/-SD, p=0.0010). An inverse association was observed in SI (GCC+, 5.76+/-2.12 and GCC-, 5.26+/-1.46, p=0.0034) and YEM (GCC+, 347+/-165 and GCC-, 305+/-110, mm Hg.mm, p=0.0005). Associations remained significant when adjusted to age, BMI, smoking and serum lipids as well as fasting glucose and insulin levels. The genetic effect size for these parameters was not significant in women.

CONCLUSIONS

IL10 promoter region high- to intermediate-producer haplotype GCC associates with decreased arterial elasticity in men. These results are in disconcordance with the supposed antiatheromatous properties of IL-10.

摘要

目的

炎症因子可改变冠心病的发病风险。细胞因子白细胞介素-10(IL-10)具有多效性,被认为可改变动脉粥样硬化的发病风险。IL-10 基因启动子区域遗传多态性与 IL-10 产生的变化有关。本研究旨在探讨白细胞介素-10 基因(IL10)的单碱基置换多态性-1082 G>A(rs1800896)、-819 C>T(rs1800871)和-592 C>A(rs1800872)是否与年轻人群的动脉粥样硬化危险因素和早期标志物相关。

方法和结果

作为年轻芬兰人心血管风险研究的一部分,我们测定了 2260 名 24-39 岁受试者的颈动脉顺应性(CAC)、僵硬度指数(SI)和杨氏弹性模量(YEM)、内膜中层厚度(IMT)、IL10 基因型和动脉粥样硬化风险参数。在男性中,IL-10 高-中产物单倍型-1082 G;-819 C;-592 C(GCC+,1.96+/-0.67)携带者的 CAC 低于非携带者(GCC-,2.10+/-0.62,%/10mmHg,均值+/-标准差,p=0.0010)。我们观察到 SI(GCC+,5.76+/-2.12;GCC-,5.26+/-1.46,p=0.0034)和 YEM(GCC+,347+/-165;GCC-,305+/-110,mm Hg·mm,p=0.0005)也存在负相关。在校正年龄、BMI、吸烟和血清脂质以及空腹血糖和胰岛素水平后,这些相关性仍然显著。在女性中,这些参数的遗传效应大小无统计学意义。

结论

IL10 启动子区域高-中产物单倍型 GCC 与男性动脉弹性降低相关。这些结果与 IL-10 抗动脉粥样硬化的假定特性不一致。

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