BASIC AND TRANSLATIONAL RESEARCH

Extended report

Genetic polymorphisms of the matrix metalloproteinase-3 (MMP-3) and tissue inhibitors of matrix metalloproteinases-1 (TIMP-1) modulate the development of ankylosing spondylitis

J C-C Wei^1,2, H-S Lee^3,4, W-C Chen³, L-J Shiu⁴, S-F Yang⁵, R-H Wong^3,4,6

¹ Department of Medicine, Chung Shan Medical University, Taichung, Taiwan
² Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
³ Department of Public Health, College of Health Care and Management, Chung Shan Medical University, Taichung, Taiwan
⁴ Institute of Public Health, College of Health Care and Management, Chung Shan Medical University, Taichung, Taiwan
⁵ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
⁶ Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan

^{Correspondence to} Dr R-H Wong, Department of Public Health, Chung Shan Medical University, 110 Chien-Kuo N Rd, Sec 1, Taichung, Taiwan 40242; rueyhong{at}csmu.edu.tw

Background: 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).

Objective: To evaluate the effects of the MMP-3 -1171 and TIMP-1 372 T>C polymorphisms on the modified risk of AS.

Methods: 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.

Results: 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.

Conclusion: The findings highlight the importance of the MMP-3 and TIMP-1 genes as crucial elements in AS development.

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