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The interaction effects between TLR4 and MMP9 gene polymorphisms contribute to aortic aneurysm risk in a Chinese Han population.

ABSTRACT: BACKGROUND:A cross-talk between Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) plays a vital role in aortic pathophysiology. The objective of this study was to evaluate the interactions between TLR4 and MMP9 polymorphisms in the risk of aortic aneurysm (AA) and its subtypes. METHODS:KASP method was used to detect polymorphisms of TLR4 (rs11536889 and rs1927914) and MMP9 (rs17576) in 472 AA patients and 498 controls. According to location and size, AA patients were further classified into abdominal AA (AAA), thoracic AA (TAA), and large AA (>5.0?cm), small AA(?5.0?cm), respectively. RESULTS:The significant interaction effect of TLR4rs1927914 with MMP9rs17576 polymorphisms was observed for the risk of TAA (Pinteraction?=?0.038, OR?=?6.186) and large AA (Pinteraction?=?0.044, OR?=?5.892). There were epistatic effects between TLR4rs1927914 and MMP9rs17576 polymorphisms on the risk of overall AA, AAA, TAA and large AA when they were present together. Moreover, the cumulative effects of the pairwise interaction TLR4rs1927914-MMP9rs17576 were associated with an increased risk of overall AA (Ptrend?=?0.032) and AAA (Ptrend?=?0.031). CONCLUSIONS:The novel interaction between TLR4rs1927914 and MMP9rs17576 polymorphisms could increase the risk of AA disease or its subtypes by exerting epistatic and cumulative effects.

SUBMITTER: Li T

PROVIDER: S-EPMC6439981 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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The interaction effects between TLR4 and MMP9 gene polymorphisms contribute to aortic aneurysm risk in a Chinese Han population.

Li Tan T Zhang Xu X Sang Liang L Li Xin-Tong XT Sun Hai-Yang HY Yang Jun J Yuan Yuan Y

BMC cardiovascular disorders 20190329 1

<h4>Background</h4>A cross-talk between Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) plays a vital role in aortic pathophysiology. The objective of this study was to evaluate the interactions between TLR4 and MMP9 polymorphisms in the risk of aortic aneurysm (AA) and its subtypes.<h4>Methods</h4>KASP method was used to detect polymorphisms of TLR4 (rs11536889 and rs1927914) and MMP9 (rs17576) in 472 AA patients and 498 controls. According to location and size, AA patients we ...[more]

PMID: 30922233

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Project description:BackgroundInflammation may be involved in the pathogenesis of acute aortic dissection (AAD). Toll-like receptor 4 (TLR4) is known to play a critical role in regulating the immune and inflammatory processes. To date, the relationship between genetic variation of TLR4 and AAD is far from clear. The purpose of our study was to illustrate the relevance of TLR4 polymorphisms with the susceptibility to AAD.MethodsA total of 222 AAD patients and 222 controls were enrolled in this study. Frequency distributions of TLR4 polymorphisms (rs10759932 in the promoter and rs11536889 in the 3'-untranslated region) were determined by the KASP method. Clinical parameters were acquired from subjects' medical records, and serum TLR4 levels were collected from our previously published data.ResultsWe found that rs10759932 polymorphism was associated with a reduced risk of AAD in the overall population (CC vs. TT: OR = 0.393, 95%CI = 0.164-0.939, P = 0.036; recessive model: OR = 0.439, 95%CI = 0.196-0.984, P = 0.045) and subgroup analyses stratified by sex. The GC genotype and dominant model of rs11536889 conferred a significantly higher risk of AAD compared with GG genotype in female subjects (GC vs. GG: OR = 3.382, 95%CI = 1.051-10.885, P = 0.041; dominant model: OR = 3.043, 95%CI = 1.041-8.900, P = 0.042). In addition, a significant interaction between the rs11536889 recessive model and dyslipidemia was observed for an increased risk of AAD (P interaction = 0.038, OR = 15.229) after the adjustment for potential clinical covariates. We also used the false-positive report probability (FPRP) analysis to validate the significant results. Furthermore, rs11536889 polymorphism could affect the maximal aortic diameters of AAD (P = 0.037), while AAD patients carrying CC genotype of rs10759932 showed lower serum TLR4 levels than TT genotype carriers (P = 0.043).ConclusionsOur findings provide evidence for the association between TLR4 polymorphisms and AAD susceptibility in a Chinese Han population, which may have some implications for understanding the role of TLR4 in the pathophysiology of AAD.

Dataset Information

The interaction effects between TLR4 and MMP9 gene polymorphisms contribute to aortic aneurysm risk in a Chinese Han population.

Publications

The interaction effects between TLR4 and MMP9 gene polymorphisms contribute to aortic aneurysm risk in a Chinese Han population.

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