CD14基因C(-260)→T多态性、可溶性内毒素受体CD14的血浆水平、它们与慢性感染的关联以及稳定型冠状动脉疾病的风险

CD14 C(-260)-->T polymorphism, plasma levels of the soluble endotoxin receptor CD14, their association with chronic infections and risk of stable coronary artery disease.

作者信息

Koenig Wolfgang, Khuseyinova Natalie, Hoffmann Michael M, März Winfried, Fröhlich Margit, Hoffmeister Albrecht, Brenner Hermann, Rothenbacher Dietrich

机构信息

Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany.

出版信息

J Am Coll Cardiol. 2002 Jul 3;40(1):34-42. doi: 10.1016/s0735-1097(02)01937-x.

DOI:10.1016/s0735-1097(02)01937-x

PMID:12103253

Abstract

OBJECTIVES

We sought to investigate the association of CD14 genotype and plasma levels of soluble (s)CD14 with risk of stable coronary artery disease (CAD), chronic infections and sensitive markers of systemic inflammation.

BACKGROUND

It has been suggested that genetic variation of the CD14 receptor with increased CD14 gene expression might play a role in atherogenesis. A mechanistic link would consist in its contribution to the inflammatory response seen in this disease.

METHODS

We measured levels of sCD14 (microg/ml; ELISA) in 312 patients with angiographically proven CAD and stable angina pectoris, and in 477 age- and gender-matched healthy blood donors. CD14 genotype was determined by polymerase chain reaction. In addition, seropositivity to Chlamydia pneumoniae and Helicobacter pylori, a complete lipid profile and various sensitive systemic markers of inflammation were measured.

RESULTS

CD14 C(-260)-->T genotype was not independently associated with increased risk of CAD after multivariable adjustments (odds ratio [OR] 1.34; 95% confidence interval [CI] 0.84 to 2.16). However, sCD14 plasma levels were higher in subjects with TT genotype compared with those with CT or CC genotype (p = 0.005). Plasma levels were not different between cases and controls (4.2 +/- 1.3 microg/ml vs. 4.3 +/- 1.3 microg/ml, p = NS). In multivariable logistic regression, the OR for the presence of CAD was 1.11 (95% CI, 0.65 to 1.91) if the top quintile of the sCD14 distribution was compared with the bottom quintile. There was no consistent association between seropositivity to either C. pneumoniae or H. pylori, or both, and sCD14 levels and between sCD14 levels or CD14 genotype and the various markers of inflammation.

CONCLUSIONS

These results do not confirm an independent relationship between CD14 genotypes or plasma levels of sCD14 and risk of stable CAD in this population.

摘要

目的

我们试图研究CD14基因分型及可溶性（s）CD14血浆水平与稳定型冠状动脉疾病（CAD）、慢性感染及全身炎症敏感标志物风险之间的关联。

背景

有研究表明，CD14受体的基因变异及CD14基因表达增加可能在动脉粥样硬化形成中起作用。其作用机制可能与其在该疾病中引发的炎症反应有关。

方法

我们检测了312例经血管造影证实患有CAD且有稳定型心绞痛的患者以及477名年龄和性别匹配的健康献血者的sCD14水平（微克/毫升；酶联免疫吸附测定法）。通过聚合酶链反应确定CD14基因分型。此外，还检测了肺炎衣原体和幽门螺杆菌的血清阳性情况、完整血脂谱以及多种炎症敏感全身标志物。

结果

多变量调整后，CD14 C（-260）→T基因分型与CAD风险增加无独立相关性（优势比[OR] 1.34；95%置信区间[CI] 0.84至2.16）。然而，TT基因型受试者的sCD14血浆水平高于CT或CC基因型受试者（p = 0.005）。病例组和对照组的血浆水平无差异（4.2±1.3微克/毫升对4.3±1.3微克/毫升，p =无显著性差异）。在多变量逻辑回归分析中，若将sCD14分布的最高五分位数与最低五分位数进行比较，CAD存在的OR为1.11（95% CI，0.65至1.91）。肺炎衣原体或幽门螺杆菌或两者血清阳性与sCD14水平之间，以及sCD14水平或CD14基因分型与多种炎症标志物之间均无一致关联。