Alp Ebru, Menevse Sevda, Tulmac Murat, Yilmaz Akin, Yalcin Ridvan, Cengel Atiye
Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
Genet Test Mol Biomarkers. 2011 Apr;15(4):193-202. doi: 10.1089/gtmb.2010.0113. Epub 2010 Dec 12.
The matrix metalloproteinase (MMP) family are key enzymes involved in the breakdown of the extracellular matrix in normal physiological processes, including tissue remodeling, and disease processes, such as arthritis and metastasis. The promoter polymorphism in the MMP2 gene may be responsible for multiple diseases related to extracellular matrix degradation. Therefore, we aimed to investigate the relationship between genotypes or haplotypes of -1575 G/A, -1306 C/T, -790 T/G, and -735 C/T promoter polymorphisms and coronary artery disease (CAD) with or without myocardial infarction (MI) history. This study included 298 patients with angiographically confirmed CAD and 299 age matched controls. Genomic DNA was isolated from whole blood and genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. No significant associations were found between -1575 G/A, -1306 C/T, and -790 T/G polymorphisms and CAD with or without MI history. However, the frequency of the -735 TT genotype was significantly lower in the controls than in the patients with MI alone when compared with the CC genotype (p=0.021). Only the distribution of the ACGC haplotype in CAD patients exhibited a significant difference than that in controls (p<0.05). The distribution of other haplotypes did not differ between CAD patients and controls. The present investigation is the first report to detect an association between MMP2 promoter polymorphisms and CAD with or without MI history in the Turkish population. Further case-control studies in CAD development might be contributed to clarify the role of these polymorphisms.
基质金属蛋白酶（MMP）家族是在正常生理过程（包括组织重塑）以及疾病过程（如关节炎和转移）中参与细胞外基质降解的关键酶。MMP2基因的启动子多态性可能与多种与细胞外基质降解相关的疾病有关。因此，我们旨在研究-1575 G/A、-1306 C/T、-790 T/G和-735 C/T启动子多态性的基因型或单倍型与有或无心肌梗死（MI）病史的冠状动脉疾病（CAD）之间的关系。本研究纳入了298例经血管造影证实的CAD患者和299例年龄匹配的对照。从全血中分离基因组DNA，并采用聚合酶链反应-限制性片段长度多态性方法进行基因分型。在有或无MI病史的CAD患者中，未发现-1575 G/A、-1306 C/T和-790 T/G多态性与CAD之间存在显著关联。然而，与CC基因型相比，对照组中-735 TT基因型的频率显著低于仅患有MI的患者（p=0.021）。仅CAD患者中ACGC单倍型的分布与对照组相比存在显著差异（p<0.05）。CAD患者和对照组之间其他单倍型的分布没有差异。本研究是首次报道在土耳其人群中检测到MMP2启动子多态性与有或无MI病史的CAD之间的关联。进一步针对CAD发生的病例对照研究可能有助于阐明这些多态性的作用。
