TLR4 and MMP2 polymorphisms and their associations with cardiovascular risk factors in susceptibility to aortic aneurysmal diseases

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.

Identification of Hub Genes and MicroRNAs Associated With Idiopathic Pulmonary Arterial Hypertension by Integrated Bioinformatics Analyses

“…MMP2 is a proteolytic enzyme that contributes to vascular protein degradation and aortic wall destruction ( Longo et al, 2002 ; Li et al, 2019 ). Much evidence suggest that MMP2 is associated with an increased risk of cardiovascular diseases, such as myocardial infarction ( Alp et al, 2011 ) and degenerative mitral valve disease ( Balistreri et al, 2016 ).…”

Risk of aortic dissection in patients with ascending aorta aneurysm: a new biological, morphological, and biomechanical network behind the aortic diameter

“…Interestingly, recent evidences showed that the immune system and inflammatory related genes have an important role in the onset and progression of sporadic TAAs even at small aortic sizes. Among these inflammatory mediators, the Toll-like receptor 4 (TLR-4) is one of the most important player [36][37][38] . The activation of TLR-4-mediated signaling pathway, both on endothelial cells (ED) and vascular smooth muscle cells (VSMCs) [39,40] , could determine the deregulation of angiotensin converting enzyme (ACE) [41][42][43] , nitric oxide (NO) [44] , metalloproteinases (MMP) [45][46][47][48] associated with endothelium dysfunction, extracellular matrix remodeling, and chronic inflammation causing medial degeneration in sporadic TAA [Figure 4].…”

The association of toll-like receptor 4 gene polymorphisms with primary open angle glaucoma susceptibility: a meta-analysis

“…In multiple sclerosis patients and experimental autoimmune encephalomyelitis models, the TLR4 was up-regulated and HMGB-1, a TLR4 ligand, plays a role in the disease progression [49][50][51]. Additionally, TLR4 polymorphisms are associated with various inflammatory diseases such as aortic aneurysmal disease, periodontitis, psoriasis arthritis, and Crohn's disease [52][53][54][55].…”