title: SNP-SNP Interaction between TLR4 and MyD88 in Susceptibility to Coronary Artery Disease in the Chinese Han Population.
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.
authors.affiliation: Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. dan_101912@163.com.|Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, China. dan_101912@163.com.|Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. dan_101912@163.com.
authors.forename: Dandan
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. lipingsun@hotmail.com.|Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, China. lipingsun@hotmail.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. xuqian820101@163.com.|Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, China. xuqian820101@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. gongyueh75@163.com.|Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, China. gongyueh75@163.com.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. wanghonghuzgykd@126.com.
authors.forename: Honghu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. junyang63@sina.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. yyuan@mail.cmu.edu.cn.|Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, China. yyuan@mail.cmu.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D044466:Asian People; D015415:Biomarkers / Q000097:blood; D002681:China / Q000453:epidemiology; D003324:Coronary Artery Disease / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D006949:Hyperlipidemias / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012307:Risk Factors; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000097:blood*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: Interaction; coronary artery disease; myeloid differentiation factor 88; polymorphism; toll-like receptor 4