Institute of Science and Technology in Medicine, Keele University, Stoke-on-Trent, Staffordshire, UK.
Genes Immun. 2012 Jan;13(1):29-37. doi: 10.1038/gene.2011.46. Epub 2011 Jul 14.
Matrix metalloproteinases (MMPs) are involved in joint destruction in rheumatoid arthritis (RA), and are strongly associated with levels of inflammation. To understand the relationship between MMP-1 and -3 variants and MMP levels in RA, we investigated the genotypic and haplotypic relationships of the MMP-1 and -3 genes with circulating levels of these MMPs. The genotypes of single-nucleotide polymorphisms (SNPs) rs1799750 (1G/2G, MMP-1 promoter), rs495366 (G/A, intergene), rs679620 (A/G, MMP-3 coding region) and rs3025058 (5A/6A, MMP-3 promoter) were determined in 430 RA patients. Each polymorphism was associated with serum levels of MMP-1 (P trend <0.0001 for each SNP), with haplotype 1G-G-A-5A associated with the highest level. The intergenic and MMP-3 SNPs were associated with MMP-1 levels independent of the MMP-1 promoter SNP. The MMP-3 SNPs were associated with serum MMP-3 level (P trend <0.0001 for each SNP), and were each associated with mean time-averaged disease activity (DAS28) in patients followed up for 2 years (P=0.003). Our findings indicate that several closely linked polymorphisms in the MMP-1-MMP-3 loci have an important role in determining the circulating levels of these MMPs in RA, and that MMP-3 polymorphism is associated with the level of disease activity over time.
基质金属蛋白酶（MMPs）参与类风湿关节炎（RA）中的关节破坏，并且与炎症水平密切相关。为了了解 MMP-1 和 -3 变体与 RA 中 MMP 水平之间的关系，我们研究了 MMP-1 和 -3 基因的基因型和单倍型与这些 MMP 循环水平之间的关系。在 430 名 RA 患者中确定了单核苷酸多态性（SNP）rs1799750（1G/2G，MMP-1 启动子）、rs495366（G/A，基因间）、rs679620（A/G，MMP-3 编码区）和 rs3025058（5A/6A，MMP-3 启动子）的基因型。每个 SNP 与 MMP-1 血清水平相关（P 趋势<0.0001），1G-G-A-5A 单倍型与最高水平相关。基因间和 MMP-3 SNP 与 MMP-1 水平相关，与 MMP-1 启动子 SNP 无关。MMP-3 SNP 与 MMP-3 血清水平相关（P 趋势<0.0001），并与随访 2 年的患者的平均时间平均疾病活动度（DAS28）相关（P=0.003）。我们的研究结果表明，MMP-1-MMP-3 基因座中的几个紧密连锁的多态性在确定 RA 中这些 MMP 的循环水平方面具有重要作用，并且 MMP-3 多态性与疾病活动度随时间的变化有关。
