TIMP-2 SNPs rs7342880 and rs4789936 are linked to risk of knee osteoarthritis in the Chinese Han Population.

Pengcheng Xu,Shuzheng Wen,Zengtao Hao,Tianbo Jin,Jieli Du,Dong Jiang,Jianzhong Wang,Jihong Wang,Shangfei Jing,Chaoqian Han,Wen Guo,Dongsheng Fan

doi:10.18632/oncotarget.13590

Pengcheng Xu, Shuzheng Wen + Show 10 more

Open Access

https://doi.org/10.18632/oncotarget.13590

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Abstract

This study aimed to investigate whether functional polymorphisms in the tissue inhibitors of metalloproteinase-2 (TIMP-2) gene are associated with susceptibility to knee osteoarthritis (OA) in the Chinese Han population. Six TIMP-2 single nucleotide polymorphisms (SNPs) were assayed using MassARRAY in 300 patients clinically and radiographically diagnosed with knee OA and in 428 controls. Allelic and genotypic frequencies were compared between groups. Logistic regression adjusting for age and gender was used to estimate risk associations between specific genotypes and knee OA by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that allele “A” in rs7342880 was significantly associated with increased risk of knee OA (OR = 1.44, 95%CI = 1.09-1.91, p = 0.035). In addition, in the over-dominant model, rs4789936 correlated with reduced risk of knee OA, adjusting for age and gender (OR = 0.69, 95%CI = 0.49-0.98, p = 0.036). Finally, rs7342880 correlated with increased risk of knee OA in females. This study provides evidence that TIMP-2 is a knee OA susceptibility gene in the Chinese population and a potential diagnostic and preventive marker for the disease.

Highlights

Knee osteoarthritis (OA) is the most common type of arthritis and a leading cause of chronic disability
This study aimed to investigate whether functional polymorphisms in the tissue inhibitors of metalloproteinase-2 (TIMP-2) gene are associated with susceptibility to knee osteoarthritis (OA) in the Chinese Han population
We used χ2 test to compare the differences in frequency distributions of alleles between cases and controls and found just one significant single nucleotide polymorphisms (SNPs) in the tissue inhibitors of metalloproteases (TIMPs)-2 gene at a 5% level

Summary

Introduction

Knee osteoarthritis (OA) is the most common type of arthritis and a leading cause of chronic disability. It affects 10% of men and 18% of women over 60 years of age and leads to substantial cost to the individual and society [1,2,3]. Metalloproteinase family proteins (MMPs) control ECM integrity by catalyzing the degradation of structural proteins including laminin, fibronectin, and various types of collagen [5, 6]. The degradation of structural proteins in cartilage, which is a feature of arthritic diseases, is accelerated by increased expression of MMPs by chondrocytes [7]. Osteoarthritic cartilage is characterized by an imbalance between MMPs and TIMPs

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