SNP-SNP Interaction between TLR4 and MyD88 in Susceptibility to Coronary Artery Disease in the Chinese Han Population.

Dandan Sun,Yuehua Gong,Qian Xu,Liping Sun,Honghu Wang,Jun Yang,Yuan Yuan

doi:10.3390/ijerph13030278

Abstract

The toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-dependent signaling pathway plays a role in the initiation and progression of coronary artery disease (CAD). We investigated SNP–SNP interactions between the TLR4 and MyD88 genes in CAD susceptibility and assessed whether the effects of such interactions were modified by confounding risk factors (hyperglycemia, hyperlipidemia and Helicobacter pylori (H. pylori) infection). Participants with CAD (n = 424) and controls (n = 424) without CAD were enrolled. Polymerase chain restriction-restriction fragment length polymorphism was performed on genomic DNA to detect polymorphisms in TLR4 (rs10116253, rs10983755, and rs11536889) and MyD88 (rs7744). H. pylori infections were evaluated by enzyme-linked immunosorbent assays, and the cardiovascular risk factors for each subject were evaluated clinically. The significant interaction between TLR4 rs11536889 and MyD88 rs7744 was associated with an increased CAD risk (p value for interaction = 0.024). In conditions of hyperglycemia, the interaction effect was strengthened between TLR4 rs11536889 and MyD88 rs7744 (p value for interaction = 0.004). In hyperlipidemic participants, the interaction strength was also enhanced for TLR4 rs11536889 and MyD88 rs7744 (p value for interaction = 0.006). Thus, the novel interaction between TLR4 rs11536889 and MyD88 rs7744 was related with an increased risk of CAD, that could be strengthened by the presence of hyperglycemia or hyperlipidemia.

Highlights

Coronary artery disease (CAD) is the most common cause of morbidity and mortality in China [1].It is a complex disease determined by genetic predisposition and environmental factor accumulation, which play major roles in a number of associated vessel wall abnormalities [2]
We found that of the polymorphisms in Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88), the TLR4 rs10116253 polymorphism was associated with a slightly decreased risk of CAD, whereas there was no overall genetic effect for TLR4 rs10983755, TLR4
Rs11536889 or MyD88 rs7744 relating to CAD risk

Summary

Introduction

Coronary artery disease (CAD) is the most common cause of morbidity and mortality in China [1]. It is a complex disease determined by genetic predisposition and environmental factor accumulation, which play major roles in a number of associated vessel wall abnormalities [2]. A person’s genetic make-up as well as other well-known major risk factors are important for the initiation and progression of CAD. A substantial body of literature has investigated the association of CAD with gene polymorphisms [3,4,5]. Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88), which act as the gate of the innate immune system and the trigger of the adaptive immune system, have been extensively. Public Health 2016, 13, 278; doi:10.3390/ijerph13030278 www.mdpi.com/journal/ijerph

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