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
Cardiovascular Genome Center, Yonsei University, Seoul, Korea.
Transl Res. 2008 Mar;151(3):154-61. doi: 10.1016/j.trsl.2007.11.004. Epub 2008 Jan 2.
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.
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。