Tumor 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.
Department of Cardiovascular Ultrasound, the First Hospital of China Medical University, Shenyang 110001, China.
Biosci Rep. 2019 Jan 8;39(1). doi: 10.1042/BSR20181591. Print 2019 Jan 31.
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. 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). In the overall analysis, MMP2rs2285053 TC genotype was correlated with TAA risk ( = 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 ( = 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. TLR4 and MMP2 polymorphisms and their complex interactions with cardiovascular risk factors contributed to aortic aneurysmal diseases.
Toll 样受体 4（TLR4）和基质金属蛋白酶 2（MMP2）在主动脉病理生理学中发挥重要作用。我们旨在评估 TLR4 和 MMP2 多态性各自以及基因与风险因素之间的复杂相互作用对主动脉瘤（AA）及其亚型易感性的贡献。采用 KASP 方法检测 498 例对照和 472 例 AA 患者（包括 212 例腹主动脉瘤（AAA）和 216 例胸主动脉瘤（TAA））中 TLR4rs11536889、rs1927914 和 MMP2rs2285053 多态性。在总体分析中，MMP2rs2285053 TC 基因型与 TAA 风险相关（ = 0.047，OR = 1.487）。分层分析显示，TLR4rs1927914 TC 基因型与男性 AA 风险增加相关，而 MMP2rs2285053 TC 基因型赋予≤60 岁患者 AA 风险升高，且其 TC 基因型和显性模型与≤60 岁患者的 TAA 相关。TLR4rs1927914 与 MMP2rs2285053 之间的相互作用与 AAA 风险相关（ = 0.028，OR = 2.913）。此外，还观察到 TLR4rs11536889 与血脂异常之间存在显著的 TAA 风险相互作用，而 TLR4rs1927914 可与高血压和糖尿病相互作用，增加 AA 或其亚型的风险。TLR4rs1927914 和 MMP2rs2285053 的双向相互作用效应因糖尿病或血脂异常而增强。TLR4 和 MMP2 多态性及其与心血管危险因素的复杂相互作用与主动脉瘤疾病有关。
