Toll样受体4（TLR4）与基质金属蛋白酶9（MMP9）基因多态性之间的相互作用影响中国汉族人群患主动脉瘤的风险。
The interaction effects between TLR4 and MMP9 gene polymorphisms contribute to aortic aneurysm risk in a Chinese Han population.
作者信息
Li Tan, Zhang Xu, Sang Liang, Li Xin-Tong, Sun Hai-Yang, Yang Jun, Yuan Yuan
机构信息
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.
Department of Cardiovascular Ultrasound, the First Hospital of China Medical University, Shenyang, 110001, China.
出版信息
BMC Cardiovasc Disord. 2019 Mar 29;19(1):72. doi: 10.1186/s12872-019-1049-8.
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 = 0.038, OR = 6.186) and large AA (P = 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 = 0.032) and AAA (P = 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.
背景
Toll样受体4（TLR4）与基质金属蛋白酶9（MMP9）之间的相互作用在主动脉病理生理学中起着至关重要的作用。本研究的目的是评估TLR4和MMP9基因多态性之间的相互作用与主动脉瘤（AA）及其亚型风险的关系。
方法
采用竞争性等位基因特异性PCR（KASP）方法检测472例AA患者和498例对照者中TLR4（rs11536889和rs1927914）和MMP9（rs17576）的基因多态性。根据位置和大小，AA患者进一步分为腹主动脉瘤（AAA）、胸主动脉瘤（TAA），以及大AA（>5.0 cm）、小AA（≤5.0 cm）。
结果
观察到TLR4 rs1927914与MMP9 rs17576基因多态性之间存在显著的交互作用，对TAA风险（P = 0.038，OR = 6.186）和大AA风险（P = 0.044，OR = 5.892）有影响。当TLR4 rs1927914和MMP9 rs17576基因多态性同时存在时，它们对总体AA、AAA、TAA和大AA风险存在上位效应。此外，TLR4 rs1927914-MMP9 rs17576的成对交互作用的累积效应与总体AA（P = 0.032）和AAA（P = 0.031）风险增加相关。
结论
TLR4 rs1927914与MMP9 rs17576基因多态性之间的新型相互作用可通过上位效应和累积效应增加AA疾病或其亚型的风险。
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