Toll-like receptor 4 rs11536889 is associated with angiographic extent and severity of coronary artery disease in a Chinese population.

Dandan Sun,Hong Yan,Jun Yang,Honghu Wang,Yupeng Wu,Wen Liu

doi:10.18632/oncotarget.14014

Dandan Sun, Hong Yan + Show 4 more

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https://doi.org/10.18632/oncotarget.14014

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Journal: Oncotarget	Publication Date: Dec 18, 2016
Citations: 8	License type: cc-by

Affiliation: First Hospital of China Medical University

Abstract

Toll-like receptor 4 (TLR4) is a key modulator in many inflammation-related diseases. Polymorphisms in the TLR4 gene may alter TLR4 expression and affect the extent and severity of coronary artery disease (CAD). We analyzed 3 polymorphisms of TLR4 in 607 Chinese subjects who underwent coronary arteriography. Blood samples were collected to identify the polymorphisms. We evaluated the relationships between the polymorphisms and the number of vessels involved in coronary stenosis, Gensini scores, and Duke prognostic scores. We found that rs11536889 was associated with an increased risk of 3-vessel disease. When subjects with 3-vessel disease were compared to subjects with nonsignificant CAD, rs11536889 variant genotypes were associated with an increased risk of 3-vessel disease (GC/CC vs. GG: OR=2.06, 95%CI=1.21-3.51). When subjects with 3-vessel disease were compared to subjects with 1-vessel disease, rs11536889 variant genotypes were associated with an increased risk of 3-vessel disease (GC vs. GG: OR=2.14, 95%CI=1.20-3.79; GC/CC vs. GG: OR=2.06, 95%CI=1.20-3.54). When subjects with 3-vessel disease were compared to subjects with non-3-vessel disease, rs11536889 variant genotypes were associated with an increased risk of 3-vessel disease (GC vs. GG: OR=1.76, 95%CI=1.12-2.75; GC/CC vs. GG: OR=1.83, 95%CI=1.19-2.82). The TLR4 rs11536889 polymorphism was also related to Gensini score (P=0.02). The Gensini score was higher in subjects with the variant CC and GC/CC genotype than in subjects with the wild GG genotype (61.28 1.84 and 57.6434.82 vs. 51.2734.57). Our results demonstrate that TLR4 rs11536889 polymorphism is a novel genetic factor in the development of CAD, influencing the extent and severity of CAD.

Highlights

Coronary artery disease (CAD) is a leading cause of death worldwide
The odds ratios (ORs) and 95% confidence intervals (CIs) for Toll-like receptor 4 (TLR4) tag-single nucleotide polymorphisms (SNPs) and the number of vessels involved in coronary stenosis are shown in Effect of TLR4 polymorphisms on Gensini score
Www.impactjournals.com/oncotarget polymorphism of TLR4 is related to the extent and severity of CAD

Summary

Introduction

Coronary artery disease (CAD) is a leading cause of death worldwide. The extent and severity of CAD is correlated with mortality and longevity [1]. Substantial clinical data have illustrated that inflammation is an important etiological mechanism underlying CAD and contributes to the extent and severity of the disease [2]. Toll-like receptor (TLR) 4 is one of the most wellcharacterized inflammation-related molecules in the immune system; it is closely related to the extent and severity of CAD. Mizoguchi et al showed that TLR4 expression on peripheral venous blood monocytes was positively correlated with Gensini score in a CAD population [3]. The expression of inflammatory cytokines induced by TLR4 is significantly related to the degree of coronary stenosis within CAD patient groups [7]

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