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白细胞介素-6 受体基因多态性调节白细胞介素-6 水平和代谢综合征:GBCS-CVD。

Interleukin-6 receptor gene polymorphism modulates interleukin-6 levels and the metabolic syndrome: GBCS-CVD.

机构信息

Guangzhou Occupational Disease Prevention and Treatment Centre, Guangzhou No.12 Hospital, Guangzhou, China.

出版信息

Obesity (Silver Spring). 2010 Oct;18(10):1969-74. doi: 10.1038/oby.2010.31. Epub 2010 Feb 25.

DOI:10.1038/oby.2010.31
PMID:20186139
Abstract

Interleukin-6 (IL-6) is a key pleiotropic cytokine that modulates the inflammatory response. Single-nucleotide polymorphisms (SNPs) within associated genes may contribute to the metabolic syndrome (MES). We examined the role of the IL-6 (rs1524107-C/T) and IL-6 receptor (IL-6R, rs8192284-A/C, Asp358Ala) SNPs in modulating IL-6 levels and the syndrome. A total of 1,979 older Chinese subjects aged 50-92 years from Guangzhou Biobank Cohort Study (GBCS) were recruited. SNPs were detected using Taqman SNP genotyping kits. IL-6 was measured using enzyme-linked immunosorbent assay. The genotype frequencies were 4.9, 33.9, and 61.3% for the IL-6 CC, CT, and TT, and 12.0, 44.9, and 43.1% for the IL-6R CC, AC, and AA, respectively. Both SNPs were in Hardy-Weinberg equilibrium. The IL-6 SNP was not associated with IL-6 levels or the MES, but was dose-dependently associated with fibrinogen levels, P = 0.049. IL-6 levels significantly decreased with increasing proportions of the IL-6R A-allele 9.8 ± 4.9, 9.3 ± 4.8, and 8.4 ± 4.3, respectively, P = 0.001. Conversely, the A-allele was associated with elevated triglyceride, P = 0.009, C-reactive protein, P = 0.047, and potentially with fasting glucose levels, P = 0.077. There was an increasing prevalence of the MES in those carrying the IL-6R CC, AC, and AA genotypes at 18.1, 21.5, 25.2%, respectively, P = 0.010. The SNP was a significant independent predictor of the MES after adjusting for general obesity, age, gender and lifestyle, and socioeconomic parameters, P = 0.023. These data, which are in accord with studies from white populations suggest the IL-6R SNP may play a role in the pathogenesis of the MES possibly through modulating IL-6 levels.

摘要

白细胞介素-6(IL-6)是一种关键的多效细胞因子,可调节炎症反应。相关基因中的单核苷酸多态性(SNP)可能导致代谢综合征(MES)。我们研究了白细胞介素-6(rs1524107-C/T)和白细胞介素-6 受体(IL-6R,rs8192284-A/C,Asp358Ala)SNP 在调节 IL-6 水平和综合征中的作用。共招募了来自广州生物银行队列研究(GBCS)的 1979 名年龄在 50-92 岁的中国老年人。使用 Taqman SNP 基因分型试剂盒检测 SNP。使用酶联免疫吸附测定法测量 IL-6。IL-6 的基因型频率分别为 4.9%、33.9%和 61.3%,IL-6R 的基因型频率分别为 12.0%、44.9%和 43.1%。两种 SNP 均处于哈迪-温伯格平衡。IL-6 SNP 与 IL-6 水平或 MES 无关,但与纤维蛋白原水平呈剂量依赖性相关,P=0.049。IL-6 水平随着 IL-6R A-等位基因比例的增加而显著降低,分别为 9.8±4.9、9.3±4.8 和 8.4±4.3,P=0.001。相反,A-等位基因与甘油三酯升高相关,P=0.009,C 反应蛋白升高,P=0.047,可能与空腹血糖水平升高相关,P=0.077。携带 IL-6R CC、AC 和 AA 基因型的人群中 MES 的患病率分别为 18.1%、21.5%和 25.2%,P=0.010。该 SNP 是 MES 的独立预测因子,经一般肥胖、年龄、性别和生活方式以及社会经济参数校正后,P=0.023。这些与白人人群研究一致的数据表明,IL-6R SNP 可能通过调节 IL-6 水平在 MES 的发病机制中发挥作用。

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