Association of MMP3 promoter 5A/6A polymorphism with stability of extracellular matrix of atherosclerotic plaque.
10.3760/cma.j.issn.1003-9406.2019.06.029
- VernacularTitle:MMP3基因启动子区多态性与动脉粥样硬化斑块细胞外基质稳定性的相关性
- Author:
Jibing DU
1
;
Yin LIU
;
Jing GAO
;
Shutao CHEN
;
Hua JIANG
;
Lili ZHAO
;
Hongliang CONG
Author Information
1. Tianjin Chest Hospital, Tianjin 300051, China. Email: dujibing@126.com.
- Publication Type:Journal Article
- MeSH:
Case-Control Studies;
Extracellular Matrix;
Genetic Predisposition to Disease;
Genotype;
Humans;
Matrix Metalloproteinase 3;
genetics;
Percutaneous Coronary Intervention;
Plaque, Atherosclerotic;
genetics;
Polymorphism, Genetic;
Promoter Regions, Genetic
- From:
Chinese Journal of Medical Genetics
2019;36(6):645-648
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To assess the association of 5A/6A polymorphism in the promoter region of MMP3 gene with the stability of extracellular matrix of atherosclerotic plaque.
METHODS:Clinical data of 776 consecutive patients undergoing percutaneous coronary intervention (PCI) was reviewed. MMP3 gene polymorphisms and serum level of MMP3 for the second admission were collected. The target gene fragment containing MMP3 promoter region was transfected into HepG2 vector cells. The influence of the polymorphism on the expression of the MMP3 gene was determined in vitro.
RESULTS:Compared with the first admission data, the proportion of mutant MMP3 genotypes (5A/5A+5A/6A) was significantly higher in patients with acute myocardial infarction (AMI) compared with the control group (37.6% vs. 24.9%, P<0.01). 64.1% of the patients carrying the 5A allele had AMI, whereas only 50.11% of those carrying the 6A allele had AMI (P<0.01). The proportion of wild-type MMP3 genotype (6A/6A) was significantly higher in the stenotic group compared with the non-restenosis group (79.5% vs. 66.5%, P<0.01). Restenosis has occurred in 9.5% of patients harboring the 5A allele compared with 16.2% in those carrying the 6A allele (P<0.01). In addition, serum level of MMP3 in the restenosis group was significantly lower than that of the non-restenosis group (P<0.01). In vitro studies confirmed that the expression of pGL2-Basic/6A was significantly lower than that of pGL2-Basic/5A.
CONCLUSION:The 5A/6A polymorphism in the promoter region of the MMP3 gene may influence its transcriptional activity and impact on the degradation or push-up of extracellular matrix, resulting in a difference in the stability of atherosclerosis plaques, which in turn may induce different pathological processes in AMI or restenosis after stenting.
