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白细胞介素-6基因572C>G多态性与韩国男性冠心病患者炎症变量的相关性

Interleukin-6-572C>G polymorphism-association with inflammatory variables in Korean men with coronary artery disease.

作者信息

Jang Yangsoo, Kim Oh Yoen, Hyun Yae Jung, Chae Jey Sook, Koh Soo Jeong, Heo Yu Mi, Choi Donghoon, Shin Dong-Jik, Huttner Kenneth, Lee Jong Ho

机构信息

Cardiovascular Genome Center, Yonsei University, Seoul, Korea.

出版信息

Transl Res. 2008 Mar;151(3):154-61. doi: 10.1016/j.trsl.2007.11.004. Epub 2008 Jan 2.

Abstract

Growing evidence suggests that polymorphisms at position -174 and -572 in interleukin-6 (IL-6) gene are associated with various manifestations of atherosclerosis. We investigated the genotype effects of IL-6 -174 and -572 polymorphisms on circulating levels of inflammatory markers in Korean men with coronary artery disease (CAD). CAD patients were subdivided into 2 groups; those patients treated without lipid-lowering drug (LLD) (n = 173) and those treated with LLD (n = 353). No significant differences existed between the 2 groups in age, body mass index, blood pressure, serum glucose, alcohol consumption, cigarette smoking, and the proportions of antihypertensive and antiplatelet therapies. IL-6 - 572 C>G polymorphism was only observed in this population. In CAD patients not taking LLD, the G/G genotype of the -572C>G polymorphism was associated with greater concentrations of IL-6 (C/C: 4.1 +/- 0.8 pg/mL, C/G: 3.7 +/- 0.7, G/G: 12.4 +/- 6.6; P = 0.031), C-reactive protein (CRP) (C/C: 1.9 +/- 0.4 mg/dL, C/G: 2.7 +/- 0.8, G/G: 10.1 +/- 3.9; P = 0.002), fibrinogen (C/C: 334 +/- 6 mg/dL, C/G: 345 +/- 13, G/G: 429 +/- 38; P = 0.003), and oxidized low-density lipoprotein (ox-LDL) (C/C: 59 +/- 2 mg/dL, C/G: 55 +/- 3, G/G: 71 +/- 6; P = 0.041) than those with C/C or C/G. However, in the LLD group, no difference existed in circulating levels of IL-6, CRP, fibrinogen, and ox-LDL across the genotype after adjustment of age. This study suggests that circulating levels of IL-6 and its related proteins such as CRP and fibrinogen are associated with genotype at a promoter polymorphism (-572C>G) of the IL-6 gene in Korean men with CAD not taking LLD. LLD, mostly statin in this study, might reduce the exaggeration of G/G genotype-raising effect on inflammatory markers.

摘要

越来越多的证据表明,白细胞介素-6(IL-6)基因中-174和-572位点的多态性与动脉粥样硬化的各种表现相关。我们研究了IL-6 -174和-572多态性的基因型对韩国冠心病(CAD)男性患者循环炎症标志物水平的影响。CAD患者被分为两组;未接受降脂药物(LLD)治疗的患者(n = 173)和接受LLD治疗的患者(n = 353)。两组在年龄、体重指数、血压、血糖、饮酒、吸烟以及抗高血压和抗血小板治疗比例方面无显著差异。IL-6 - 572 C>G多态性仅在该人群中观察到。在未服用LLD的CAD患者中,-572C>G多态性的G/G基因型与更高浓度的IL-6(C/C:4.1±0.8 pg/mL,C/G:3.7±0.7,G/G:12.4±6.6;P = 0.031)、C反应蛋白(CRP)(C/C:1.9±0.4 mg/dL,C/G:2.7±0.8,G/G:10.1±3.9;P = 0.002)、纤维蛋白原(C/C:334±6 mg/dL,C/G:345±13,G/G:429±38;P = 0.003)和氧化低密度脂蛋白(ox-LDL)(C/C:59±2 mg/dL,C/G:55±3,G/G:71±6;P = 0.041)相关,高于C/C或C/G基因型患者。然而,在LLD组中,调整年龄后,不同基因型的IL-6、CRP、纤维蛋白原和ox-LDL循环水平无差异。本研究表明,在未服用LLD的韩国CAD男性患者中,IL-6及其相关蛋白如CRP和纤维蛋白原的循环水平与IL-6基因启动子多态性(-572C>G)的基因型相关。LLD(本研究中主要为他汀类药物)可能会降低G/G基因型对炎症标志物升高作用的夸大影响。

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