Association of matrix metalloproteinase 3 promoter genotype with disease outcome in rheumatoid arthritis
Association of matrix metalloproteinase 3 promoter genotype with disease outcome in rheumatoid arthritis
复制标题
DOI：
10.1038/sj.gene.6364050
复制
发表时间：
2004-03-01
影响因子：
5
通讯作者：
Hajeer, AH
中科院分区：
文献类型：
--
作者：
Mattey, DL;Nixon, NB;Hajeer, AH
基质金属蛋白酶（MMP）参与类风湿性关节炎（RA）的关节破坏。我们调查了254例确诊的RA患者MMP-3（基质分解素-1）基因启动子区域内的5A/6A多态性是否与疾病结局相关。MMP-3 6A等位基因纯合子患者的影像学损害（Larsen评分）高于其他基因型患者（109.8 vs 91.1，P = 0.04）。6A/6A基因型患者也有更多的功能障碍和更高的血清proMMP-3水平，虽然只有后者是显着的（P = 0.002）。6A等位基因的纯合性与RA相关的HLA-DRB 1共享表位（SE）的携带之间可能存在关联。这些因素的组合与比单独SE更严重的疾病相关。这些数据表明MMP-3 6A/6A基因型与RA预后较差相关，并且这种基因型可能与SE对疾病严重程度有累加效应。
Matrix metalloproteinases (MMPs) are implicated in joint destruction in rheumatoid arthritis (RA). We investigated whether the 5A/6A polymorphism within the MMP-3 (stromelysin-1) gene promoter region is associated with disease outcome in 254 patients with established RA. Patients homozygous for the MMP-3 6A allele had more radiographic damage (measured by Larsen score) than those with other genotypes (109.8 vs 91.1, P = 0.04). Patients with the 6A/6A genotype also had more functional impairment and higher serum proMMP-3 levels, although only the latter was significant (P = 0.002). A possible association was found between homozygosity for the 6A allele and carriage of the RA-associated HLA-DRB1 shared epitope (SE). Combination of these factors was associated with more severe disease than the SE alone. The data suggest that the MMP-3 6A/6A genotype is associated with worse RA outcome, and that this genotype may have an additive effect with the SE on disease severity.