当前位置： SCI文献检索 > AMERICAN HEART JOURNAL期刊下所有文献 > Toll-like receptor 4 gene Asp299Gly polymorphism is associated with reductions in vascular inflammation, angiographic coronary artery disease, and clinical diabetes.

Toll-like receptor 4 gene Asp299Gly polymorphism is associated with reductions in vascular inflammation, angiographic coronary artery disease, and clinical diabetes.

Abstract：

BACKGROUND:Coronary artery disease (CAD) and, increasingly, diabetes are recognized as having an inflammatory basis. Membrane toll-like receptors (TLRs) activate signaling pathways that up-regulate inflammation. We evaluated whether the Asp299Gly polymorphism in the TLR4 gene, which impairs inflammatory responses, is associated with reduced vascular inflammation (assessed by C-reactive protein [CRP]) and a decreased risk for CAD and diabetes. METHODS:1894 patients without acute myocardial infarction undergoing coronary angiography were studied. Genotyping was performed by real-time polymerase chain reaction. CAD was defined as >or=70% stenosis. Diabetes was diagnosed by patients' referring physicians. CRP was measured by fluorescence polarization immunoassay. Regression analyses adjusted for traditional cardiac risk factors. RESULTS:Patients averaged 64 +/- 11 years of age, and 69% were male. Asp299Gly genotype frequencies were: AA = 0.911 (n = 1725), AG = 0.086 (n = 164), and GG = 0.003 (n = 5), in keeping with Hardy-Weinberg equilibrium. CRP was lower among G-allele carriers (median = 1.11 mg/dL) than wild-type (AA) subjects (1.23 mg/dL, adjusted P = .044). G-allele carriers also had a lower prevalence of CAD (65% vs. 73%, OR = 0.67, CI = 0.46-0.99, adjusted P = .048) and diabetes (11% vs. 18%, OR = 0.63, CI = 0.42-0.95, adjusted P = .029), which persisted in multivariate logistic regression analyses. 299Gly carriage did not affect clinical outcomes nor interact with statin therapy. CONCLUSIONS:The TLR4 299Gly allele was associated with reduced CRP levels and, in parallel, a decreased risk of angiographic CAD and clinical diabetes. These findings suggest that down-regulation of innate immune responsiveness could beneficially modify CAD and diabetes risk and might provide a novel basis for genetic risk stratification and therapeutic targeting.

journal_name

Am Heart J

journal_title

American heart journal

authors

Kolek MJ,Carlquist JF,Muhlestein JB,Whiting BM,Horne BD,Bair TL,Anderson JL

doi

10.1016/j.ahj.2004.05.049

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

1034-40

issue

eissn

0002-8703

issn

1097-6744

pii

S0002870304003692

journal_volume

148

pub_type

杂志文章

在线工具

Toll-like receptor 4 gene Asp299Gly polymorphism is associated with reductions in vascular inflammation, angiographic coronary artery disease, and clinical diabetes.