VINČA Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
Atherosclerosis. 2011 Dec;219(2):673-8. doi: 10.1016/j.atherosclerosis.2011.08.025. Epub 2011 Aug 22.
Matrix metalloproteinases (MMPs) are involved in the remodeling of the extracellular matrix in the arterial wall. Collagen I is associated with vascular smooth muscle cell (VSMC) migration and monocyte differentiation. MMP-8 is expressed in atherosclerotic plaque and preferentially cleaves collagen type I. The aim of this study was to investigate the associations of two MMP-8 promoter polymorphisms, rs11225395 (-799C/T) and rs1320632 (-381 A/G), with carotid plaque occurrence, and the influence of these polymorphisms on MMP-8 mRNA expression in plaque tissue.
The study included a total of 766 participants: 277 controls and 489 patients with carotid atherosclerosis undergoing endarterectomy. The two investigated polymorphisms were genotyped by PCR-RFLP. The gene expression analysis was performed by real-time PCR.
In females only, a significantly higher frequency of the -381G allele was found in patients with carotid atherosclerosis compared to controls (OR, 1.7; 95% CI 1.1-2.9; p = 0.001). Significant up-regulation of MMP-8 gene expression was observed in patients carrying the -381G allele compared to those with the AA genotype (mean factor, 3.54; S.E. range, 0.643-19.551; p = 0.007). Carotid plaque tissue of the haplotype G(-381)T(-799) showed a significantly higher mRNA level compared with the reference A(-381)C(-799) haplotype (p = 0.003).
Our preliminary results indicate that MMP-8 -381A/G and -799C/T gene polymorphisms could be risk factors for carotid atherosclerosis. Further validation and functional studies are needed to establish the potential regulatory role of these polymorphisms and their impact on susceptibility to carotid atherosclerosis.
基质金属蛋白酶（MMPs）参与动脉壁细胞外基质的重塑。胶原 I 与血管平滑肌细胞（VSMC）迁移和单核细胞分化有关。MMP-8 在动脉粥样硬化斑块中表达，并优先裂解胶原 I 型。本研究旨在探讨两种 MMP-8 启动子多态性，rs11225395（-799C/T）和 rs1320632（-381A/G）与颈动脉斑块发生的相关性，并研究这些多态性对斑块组织中 MMP-8mRNA 表达的影响。
本研究共纳入 766 名参与者：277 名对照组和 489 名颈动脉粥样硬化患者行内膜切除术。通过 PCR-RFLP 法检测两种研究的多态性。采用实时 PCR 法进行基因表达分析。
仅在女性中，颈动脉粥样硬化患者中 -381G 等位基因的频率明显高于对照组（OR，1.7；95%CI，1.1-2.9；p=0.001）。与 AA 基因型相比，携带 -381G 等位基因的患者 MMP-8 基因表达明显上调（平均因子，3.54；S.E.范围，0.643-19.551；p=0.007）。与参考 A(-381)C(-799) 单倍型相比，G(-381)T(-799) 单倍型的颈动脉斑块组织显示出明显更高的 mRNA 水平（p=0.003）。
我们的初步结果表明，MMP-8-381A/G 和-799C/T 基因多态性可能是颈动脉粥样硬化的危险因素。需要进一步的验证和功能研究来确定这些多态性的潜在调节作用及其对颈动脉粥样硬化易感性的影响。
