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

// Pengcheng Xu 1, * , Wen Guo 1, * , Tianbo Jin 2, 3 , Jihong Wang 4 , Dongsheng Fan 4 , Zengtao Hao 4 , Shangfei Jing 4 , ChaoQian Han 4 , Jieli Du 1 , Dong Jiang 1 , Shuzheng Wen 4 , Jianzhong Wang 5 1 Inner Mongolia Medical University, Hohhot 010010, Inner Mongolia, China 2 Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University, Xi’an, Shaanxi 710069, China 3 Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi, 710075, China 4 Department of Hand and Foot Surgery, Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia Autonomous Region, China 5 Department of Trauma, Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia Autonomous Region, China * These authors have contributed equally to this work Correspondence to: Shuzheng Wen, email: wenshuzhengdoctor@163.com Jianzhong Wang, email: wangjianzhong0503@126.com Keywords: knee osteoarthritis, TIMP-2 , single nucleotide polymorphism, gene Received: July 11, 2016     Accepted: November 09, 2016     Published: November 25, 2016 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.