Toll样受体4（TLR-4）和CD14基因分型与可溶性CD14：它们会引发冠状动脉粥样硬化吗？
TLR-4 and CD14 Genotypes and Soluble CD14: Could They Predispose to Coronary Atherosclerosis?
作者信息
Konstantinidou Maria Kalliopi, Goutas Nikos, Vlachodimitropoulos Dimitrios, Chaidaroglou Antigoni, Stefanou Demetrios, Poumpouridou Nikoleta, Mastorakou Renata, Gazouli Maria, Kyparissopoulos Dimitrios, Spiliopoulou Chara
机构信息
Department of Cardiothoracic Surgery, Royal Brompton and Harefield Trust, 156 Montreal House, Surrey Quays Road, London SE16 7AQ, UK.
Department of Forensic Medicine and Toxicology, Athens Medical School, Athens 115 27, Greece.
出版信息
J Cardiovasc Dev Dis. 2016 Mar 10;3(1):9. doi: 10.3390/jcdd3010009.
BACKGROUND
Inflammatory mechanisms are key to the pathogenesis of atherosclerosis. Functional polymorphisms of TLR-4, Asp299Gly and Thr399Ile, CD14 promoter area C260T polymorphism and plasma levels of soluble CD14 are studied in subjects with Coronary Artery Disease (CAD).
METHODS
DNA was obtained from 100 human paraffin-embedded aortic specimens, from cadavers with known coronary atheromatosis (Group A) and 100 blood samples from patients with CAD, as detected by cardiac Multi-Detector-row-Computed-Tomography (MDCT) (Group B). Our control group consisted of 100 healthy individuals (Group C). Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR). Plasma levels of sCD14 were measured with ELISA.
RESULTS
For TLR-4 Asp299Gly and Thr399Ile polymorphisms, no statistically significant differences were observed. Regarding the C260T polymorphism, frequencies of T allele were significantly higher in the control group compared to the case group ( = 0.05). The Odds Ratio (OR) showed statistically significant association of TT genotype with healthy individuals (OR 0.25, 95% Confidence Interval CI 0.10-0.62, = 0.0017). Plasma levels of sCD14 in patients with CAD (mean value = 1.35 μg/mL) were reduced when compared to reference value.
CONCLUSIONS
The studied polymorphisms ofTLR-4 showed no association with CAD. Conversely, the functional polymorphism of CD14 has a statistically significant difference in expression between healthy and affected by CAD individuals.
背景
炎症机制是动脉粥样硬化发病机制的关键。本研究旨在探讨冠状动脉疾病（CAD）患者中Toll样受体4（TLR-4）的功能多态性（Asp299Gly和Thr399Ile）、CD14启动子区域C260T多态性以及可溶性CD14的血浆水平。
方法
从100例已知冠状动脉粥样硬化的尸体石蜡包埋主动脉标本中获取DNA（A组），并从经心脏多排螺旋计算机断层扫描（MDCT）检测确诊为CAD的患者中采集100份血样（B组）。对照组为100名健康个体（C组）。采用限制性片段长度多态性聚合酶链反应（RFLP-PCR）进行基因分型，用酶联免疫吸附测定（ELISA）法检测血浆sCD14水平。
结果
对于TLR-4 Asp299Gly和Thr399Ile多态性，未观察到统计学上的显著差异。关于C260T多态性，对照组T等位基因频率显著高于病例组（P = 0.05）。优势比（OR）显示TT基因型与健康个体有统计学意义的关联（OR 0.25，95%置信区间CI 0.10 - 0.62，P = 0.0017）。与参考值相比，CAD患者血浆sCD14水平（平均值 = 1.35μg/mL）降低。
结论
所研究的TLR-4多态性与CAD无关联。相反，CD14的功能多态性在健康个体和CAD患者之间的表达存在统计学显著差异。
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