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白细胞介素-6启动子多态性及血清白细胞介素-6水平对伊尔斯病患者急性炎症和新生血管形成阶段的影响

Impact of interleukin-6 promoter polymorphism and serum interleukin-6 level on the acute inflammation and neovascularization stages of patients with Eales' disease.

作者信息

Sen Aditi, Paine Suman Kalyan, Chowdhury Imran Hussain, Mukherjee Amrita, Choudhuri Subhadip, Saha Avijit, Mandal Lakshmi Kanta, Bhattacharya Basudev

机构信息

Department of Biochemistry, Dr. B C Roy Post Graduate Institute of Basic Medical Education and Research (IPGME&R), Kolkata, India.

出版信息

Mol Vis. 2011;17:2552-63. Epub 2011 Oct 1.

PMID:22025890
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3198485/
Abstract

PURPOSE

To evaluate the role of interleukin-6 (IL-6) in the inflammatory and proliferative stages of Eales' disease (ED) and to determine the influence of IL-6-174G/C polymorphism in the IL-6 and IL-6-regulated protein expression, as well as the development of ED.

METHODS

One hundred and twenty-one patients diagnosed with ED, 223 matched healthy controls, and 16 control patients with macular holes were recruited from the eastern Indian population. Serum and vitreous levels of IL-6 and vascular endothelial growth factors (VEGF) were measured by enzyme-linked immunosorbent assay. Serum levels of high-sensitivity C-reactive protein (hsCRP) were measured by enzyme immunoassay. Subjects were genotyped for the IL-6-174G/C polymorphism (rs1800795) by a custom TaqMan single-nucleotide polymorphism (SNP) Genotyping Assays system.

RESULTS

Serum IL-6 (p<0.0001), hsCRP (p<0.0001), and VEGF (p=0.0031) levels were significantly higher in the inflammatory stage of ED than in healthy controls. Serum IL-6 also significantly correlated with hsCRP (Spearman's correlation coefficient; r=0.4992, p=0.0009), but not with VEGF in this stage in ED patients. At the proliferative stage of ED, significantly higher levels of vitreous IL-6 (p=<0.0001) and VEGF (p=<0.0001) were found compared with the vitreous of patients with macular holes. A significant correlation was observed between vitreous IL-6 and VEGF in ED patients (Spearman's correlation coefficient; r=0.5834, p=0.0087). A statistically significant association was found between the -174GG genotype (p=0.006) and occurrence of ED. Mean serum and vitreous concentrations of IL-6 were also higher in the subjects with the GG genotype than in those with the GC or CC genotype in this population.

CONCLUSIONS

IL-6 expression, regulated by the allelic distribution of -174 loci and the enhanced level of IL-6, modulates CRP and VEGF concentration depending respectively on the acute inflammatory stimulation at the initial stage and angiogenic stimulation at the advanced stage of ED.

摘要

目的

评估白细胞介素-6(IL-6)在伊尔斯病(ED)炎症和增殖阶段中的作用,并确定IL-6基因-174G/C多态性对IL-6及其调控蛋白表达以及ED发病的影响。

方法

从印度东部人群中招募了121例确诊为ED的患者、223例匹配的健康对照者以及16例黄斑裂孔对照患者。采用酶联免疫吸附测定法检测血清和玻璃体中IL-6及血管内皮生长因子(VEGF)的水平。采用酶免疫测定法检测血清高敏C反应蛋白(hsCRP)水平。通过定制的TaqMan单核苷酸多态性(SNP)基因分型检测系统对受试者进行IL-6基因-174G/C多态性(rs1800795)基因分型。

结果

ED炎症期患者血清IL-6(p<0.0001)、hsCRP(p<0.0001)和VEGF(p=0.0031)水平显著高于健康对照者。在ED患者的这一阶段,血清IL-6也与hsCRP显著相关(Spearman相关系数;r=0.4992,p=0.0009),但与VEGF无相关性。在ED增殖期,与黄斑裂孔患者的玻璃体相比,发现玻璃体中IL-6(p<0.0001)和VEGF(p<0.0001)水平显著更高。ED患者玻璃体中IL-6与VEGF之间存在显著相关性(Spearman相关系数;r=0.5834,p=0.0087)。发现-174GG基因型与ED发病之间存在统计学显著关联(p=0.006)。在该人群中,GG基因型受试者的血清和玻璃体IL-6平均浓度也高于GC或CC基因型受试者。

结论

由-174位点的等位基因分布调控的IL-6表达以及IL-6水平的升高,分别根据ED初期的急性炎症刺激和晚期的血管生成刺激来调节CRP和VEGF浓度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eb3/3198485/a56bb74913e3/mv-v17-2552-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eb3/3198485/511bef620a84/mv-v17-2552-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eb3/3198485/f3e6acbc47f4/mv-v17-2552-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eb3/3198485/44bd8c912f6b/mv-v17-2552-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eb3/3198485/a56bb74913e3/mv-v17-2552-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eb3/3198485/511bef620a84/mv-v17-2552-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eb3/3198485/f3e6acbc47f4/mv-v17-2552-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eb3/3198485/44bd8c912f6b/mv-v17-2552-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eb3/3198485/a56bb74913e3/mv-v17-2552-f4.jpg

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