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

Tan Li1,2, Xu Zhang3, Liang Sang1

  • 1Tumor 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.

BMC Cardiovascular Disorders
|March 30, 2019
PubMed
Abstract

Insights

Genetic variations in Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) interact to increase aortic aneurysm (AA) risk. This study highlights specific gene polymorphisms, TLR4rs1927914 and MMP9rs17576, as key contributors to AA development.

Area of Science:

  • Genetics
  • Cardiovascular Biology
  • Molecular Medicine

Background:

  • A complex interplay exists between Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) in the development of aortic pathophysiology.
  • Understanding these interactions is crucial for elucidating the mechanisms underlying aortic diseases.

Purpose of the Study:

  • To investigate the combined effect of specific polymorphisms in TLR4 and MMP9 on the risk of developing aortic aneurysm (AA).
  • To analyze the interaction between TLR4 (rs11536889, rs1927914) and MMP9 (rs17576) gene variants in relation to AA and its subtypes.

Main Methods:

  • Genotyping of TLR4 (rs11536889, rs1927914) and MMP9 (rs17576) polymorphisms was performed using the KASP method.
  • A cohort of 472 patients with aortic aneurysm and 498 healthy controls were analyzed.
  • Aortic aneurysm subtypes, including abdominal (AAA) and thoracic (TAA), were classified based on location and size.

Main Results:

  • A significant interaction was found between TLR4rs1927914 and MMP9rs17576 polymorphisms, increasing the risk for thoracic aortic aneurysm (TAA) and large aortic aneurysms (>5.0 cm).
  • Epistatic effects were observed between TLR4rs1927914 and MMP9rs17576 on the risk of overall AA, AAA, TAA, and large AA when variants were present together.
  • Cumulative effects of the TLR4rs1927914-MMP9rs17576 interaction were associated with elevated risks for overall AA and AAA.

Conclusions:

  • The identified interaction between TLR4rs1927914 and MMP9rs17576 polymorphisms represents a novel risk factor for aortic aneurysm.
  • Epistatic and cumulative effects of these gene variants contribute to the increased susceptibility and risk of developing AA and its subtypes.
Keywords:
Aortic aneurysmInteractionMatrix metalloproteinase 9PolymorphismToll-like receptor 4

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