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

Tan Li; Xu Zhang; Liang Sang; Xin-Tong Li; Hai-Yang Sun; Jun Yang; Yuan Yuan

doi:10.1186/s12872-019-1049-8

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

BMC Cardiovasc Disord. 2019 Mar 29;19(1):72. doi: 10.1186/s12872-019-1049-8.

Authors

Tan Li^{1

2}, Xu Zhang³, Liang Sang¹, Xin-Tong Li⁴, Hai-Yang Sun², Jun Yang², Yuan Yuan⁵

Affiliations

¹ Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, No.155 Nanjing Bei Street, Heping District, Shenyang, Liaoning Province, People's Republic of China, 110001.
² Department of Cardiovascular Ultrasound, the First Hospital of China Medical University, Shenyang, 110001, China.
³ Medical Administration Department, the First Hospital of China Medical University, Shenyang, 110001, China.
⁴ Department of Vascular and Thyroid Surgery, the First Hospital of China Medical University, Shenyang, 110001, China.
⁵ Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, No.155 Nanjing Bei Street, Heping District, Shenyang, Liaoning Province, People's Republic of China, 110001. yuanyuan@cmu.edu.cn.

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 (P_interaction = 0.038, OR = 6.186) and large AA (P_interaction = 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 (P_trend = 0.032) and AAA (P_trend = 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.

Keywords: Aortic aneurysm; Interaction; Matrix metalloproteinase 9; Polymorphism; Toll-like receptor 4.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aortic Aneurysm, Abdominal / diagnostic imaging
Aortic Aneurysm, Abdominal / ethnology
Aortic Aneurysm, Abdominal / genetics*
Aortic Aneurysm, Thoracic / diagnostic imaging
Aortic Aneurysm, Thoracic / ethnology
Aortic Aneurysm, Thoracic / genetics*
Asian People / genetics
Case-Control Studies
China / epidemiology
Epistasis, Genetic*
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Male
Matrix Metalloproteinase 9 / genetics*
Middle Aged
Phenotype
Polymorphism, Single Nucleotide*
Risk Assessment
Risk Factors
Toll-Like Receptor 4 / genetics*

Substances

TLR4 protein, human
Toll-Like Receptor 4
MMP9 protein, human
Matrix Metalloproteinase 9