TLR4 and MMP2 polymorphisms and their associations with cardiovascular risk factors in susceptibility to aortic
Tan Li1,2, Jingjing Jing1, Liping Sun1
1Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China.
Abstract:
Background: Toll-like receptor 4 (TLR4) and matrix metalloproteinase 2 (MMP2) play important roles in aortic pathophysiology. We aimed to evaluate the contribution of TLR4 and MMP2 polymorphisms individually and complex interactions between gene and risk factors in susceptibility to aortic aneurysm (AA) and its subtypes. Methods: KASP method was adopted to detect TLR4rs11536889, rs1927914 and MMP2rs2285053 polymorphisms in 498 controls and 472 AA patients, including 212 abdominal AA (AAA) and 216 thoracic AA (TAA). Results: In the overall analysis, MMP2rs2285053 TC genotype was correlated with TAA risk (P = 0.047, OR = 1.487). Stratified analysis revealed an increased AA risk in males with TLR4rs1927914 TC genotype, while MMP2rs2285053 TC conferred an elevated AA risk in the subjects ≤60 years, and its TC genotype and dominant model were associated with TAA in the subjects ≤60 year. The interaction between TLR4rs1927914 and MMP2rs2285053 was associated with AAA risk (Pinteraction = 0.028, OR = 2.913). Furthermore, significant interaction between TLR4rs11536889 and dyslipidemia was observed for TAA risk, while TLR4rs1927914 could interact with hypertension and diabetes to increase the risk of AA or its subtypes. Two-way interaction effect of TLR4rs1927914 and MMP2rs2285053 was enhanced by diabetes or dyslipidemia. Conclusion: TLR4 and MMP2 polymorphisms and their complex interactions with cardiovascular risk factors contributed to aortic aneurysmal diseases.
Insights
Genetic variations in Toll-like receptor 4 (TLR4) and matrix metalloproteinase 2 (MMP2) influence aortic aneurysm risk. Gene interactions and cardiovascular factors significantly contribute to the development of aortic aneurysms.
Area of Science:
- Cardiovascular Genetics
- Aortic Pathophysiology
- Molecular Biology
Background:
- Toll-like receptor 4 (TLR4) and matrix metalloproteinase 2 (MMP2) are implicated in the development of aortic diseases.
- Genetic polymorphisms in TLR4 and MMP2 may influence susceptibility to aortic aneurysms (AA).
Purpose of the Study:
- To investigate the individual and interactive roles of TLR4 and MMP2 gene polymorphisms in the risk of developing aortic aneurysms (AA) and its subtypes.
- To explore the complex interactions between these genetic variations and cardiovascular risk factors in AA pathogenesis.
Main Methods:
- Genotyping of TLR4 (rs11536889, rs1927914) and MMP2 (rs2285053) polymorphisms using the KASP method.
- Analysis of 498 controls and 472 AA patients, including abdominal (AAA) and thoracic (TAA) subtypes.
- Statistical evaluation of individual gene effects, gene-gene interactions, and gene-environment interactions with risk factors like hypertension, diabetes, and dyslipidemia.
Main Results:
- The MMP2 rs2285053 TC genotype was associated with an increased risk of thoracic aortic aneurysm (TAA).
- Specific TLR4 (rs1927914 TC) and MMP2 (rs2285053 TC) genotypes showed increased AA risk in males and individuals ≤60 years, respectively.
- Significant gene-gene interactions (TLR4rs1927914 and MMP2rs2285053) were linked to abdominal aortic aneurysm (AAA) risk.
- Interactions between TLR4 polymorphisms and cardiovascular risk factors (dyslipidemia, hypertension, diabetes) were observed for TAA and overall AA risk, with diabetes or dyslipidemia potentiating the combined effect of TLR4 and MMP2 variants.
Conclusions:
- Polymorphisms in TLR4 and MMP2 are associated with susceptibility to aortic aneurysmal diseases.
- Complex interactions between TLR4 and MMP2 genetic variants, as well as their interplay with cardiovascular risk factors, significantly contribute to the pathogenesis of aortic aneurysms.
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