Wei J C-C, Lee H-S, Chen W-C, Shiu L-J, Yang S-F, Wong R-H
Department of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Ann Rheum Dis. 2009 Nov;68(11):1781-6. doi: 10.1136/ard.2008.099481. Epub 2008 Nov 19.
The aetiology of ankylosing spondylitis (AS) remains unclear. Inflammation progresses to fibrosis and calcification of the spine and sacroiliac joints in AS development. Fibrosis results from excessive accumulations of the extracellular matrix (ECM). ECM turnover depends on the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs).
To evaluate the effects of the MMP-3 -1171 and TIMP-1 372 T>C polymorphisms on the modified risk of AS.
Genotypes of 241 patients with AS and 241 controls were identified by PCR. Disease activity and functional status were assessed by the Bath Ankylosing Spondylitis Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Global (BAS-G) Score.
MMP-3 6A/6A carriers had a 2.41-fold (95% confidence interval (CI) 1.55 to 3.74) increased risk of AS compared with 6A/5A and 5A/5A carriers. TIMP-1 C alleles had a greater risk of AS, but this was not significant (odds ratio (OR) = 1.28, 95% CI 0.92 to 1.77). Pairwise analysis of the MMP-3/TIMP-1 alleles showed that 6A/C (OR = 3.23, 95% CI 1.50 to 6.95) and 6A/T (OR = 2.55, 95% CI 1.17 to 5.54) had a significantly greater risk of AS than the 5A/T alleles. After adjustment for the effects of age, gender and disease duration, the MMP-3/TIMP-1 5A/T alleles had the lowest BASDAI (p = 0.02), BASFI (p = 0.05) and BAS-G (p = 0.02) among all MMP-3/TIMP-1 alleles.
The findings highlight the importance of the MMP-3 and TIMP-1 genes as crucial elements in AS development.
强直性脊柱炎（AS）的病因仍不清楚。在AS发展过程中，炎症会进展为脊柱和骶髂关节的纤维化和钙化。纤维化是由细胞外基质（ECM）过度积聚导致的。ECM的周转取决于基质金属蛋白酶（MMPs）及其组织抑制剂（TIMPs）之间的平衡。
评估MMP - 3 -1171和TIMP - 1 372 T>C基因多态性对AS修正风险的影响。
采用聚合酶链反应（PCR）鉴定241例AS患者和241例对照的基因型。通过巴斯强直性脊柱炎活动指数（BASDAI）、巴斯强直性脊柱炎功能指数（BASFI）和巴斯强直性脊柱炎整体（BAS - G）评分评估疾病活动度和功能状态。
与6A/5A和5A/5A携带者相比，MMP - 3 6A/6A携带者患AS的风险增加2.41倍（95%置信区间（CI）1.55至3.74）。TIMP - 1 C等位基因患AS的风险更高，但不显著（比值比（OR） = 1.28，95% CI 0.92至1.77）。对MMP - 3/TIMP - 1等位基因的成对分析显示，6A/C（OR = 3.23，95% CI 1.50至6.95）和6A/T（OR = 2.55，95% CI 1.17至5.54）患AS的风险显著高于5A/T等位基因。在调整年龄、性别和病程的影响后，MMP - 3/TIMP - 1 5A/T等位基因在所有MMP - 3/TIMP - 1等位基因中具有最低的BASDAI（p = 0.02）、BASFI（p = 0.05）和BAS - G（p = 0.02）。
研究结果突出了MMP - 3和TIMP - 1基因作为AS发展关键因素的重要性。
