PMID- 31208828
OWN - NLM
STAT- MEDLINE
DCOM- 20191219
LR  - 20221207
IS  - 1878-1861 (Electronic)
IS  - 1878-1861 (Linking)
VI  - 22
IP  - 10
DP  - 2019 Oct
TI  - Additional evidence supports association of common genetic variants in MMP3 and 
      TIMP2 with increased risk of chronic Achilles tendinopathy susceptibility.
PG  - 1074-1078
LID - S1440-2440(18)31312-4 [pii]
LID - 10.1016/j.jsams.2019.05.021 [doi]
AB  - OBJECTIVES: To systematically evaluate the effects of matrix metalloproteinase-3 
      (MMP3) and tissue inhibitor of metalloproteinase-2 (TIMP2) on chronic Achilles 
      tendinopathy (AT) susceptibility. Chronic AT is one of the most prevalent and 
      severe injuries in athletes. Early studies suggested that tendon extracellular 
      matrix (ECM) may be involved in the pathogenesis of chronic AT. MMP3 is an 
      important member of the MMP family and is important to ECM integrity. In 
      addition, tissue inhibitor of metalloproteinase-2 (TIMP2) can indirectly limit 
      the activity of MMP3 activity. DESIGN: Case-control genetic association study. 
      METHODS: A total of 1084 chronic AT patients and 2188 controls with Chinese Han 
      ancestry were recruited. Twenty-one SNPs, 4 mapped to MMP3 and 17 mapped to 
      TIMP2, were selected and genotyped. Genetic association analyses and eQTL 
      analyses were performed. In addition, we also examined the potential effects of 
      epistasis using a case-only study design. RESULTS: Two SNPs, rs679620 (OR=0.82, 
      P=0.0006, MMP3) and rs4789932 (OR=1.2, P=0.0002, TIMP2) were identified to be 
      significantly associated with chronic AT risk. No significant results were 
      obtained from epistasis analyses. SNP rs4789932 was identified to be strongly 
      associated with the gene expression level of TIMP2 in two types of human tissues: 
      atrial appendage (P=0.0003) and tibial artery (P=0.0009). CONCLUSIONS: We have 
      identified genetic polymorphisms in MMP3 and TIMP2 to be significantly associated 
      with chronic AT risk. Further eQTL analyses indicated that SNP rs4789932 of TIMP2 
      was related to the gene expression levels of TIMP2. These results suggest 
      important roles for MMP3 and TIMP2 in the pathophysiology of chronic AT.
CI  - Copyright (c) 2019 Sports Medicine Australia. Published by Elsevier Ltd. All rights 
      reserved.
FAU - Nie, Guanghua
AU  - Nie G
AD  - Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong 
      University, China.
FAU - Wen, Xiaodong
AU  - Wen X
AD  - Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong 
      University, China.
FAU - Liang, Xiaojun
AU  - Liang X
AD  - Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong 
      University, China.
FAU - Zhao, Hongmou
AU  - Zhao H
AD  - Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong 
      University, China.
FAU - Li, Yi
AU  - Li Y
AD  - Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong 
      University, China.
FAU - Lu, Jun
AU  - Lu J
AD  - Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong 
      University, China. Electronic address: junluhh@163.com.
LA  - eng
PT  - Journal Article
DEP - 20190607
PL  - Australia
TA  - J Sci Med Sport
JT  - Journal of science and medicine in sport
JID - 9812598
RN  - 0 (TIMP2 protein, human)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Achilles Tendon/*physiopathology
MH  - Asian People
MH  - Case-Control Studies
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Matrix Metalloproteinase 3/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Quantitative Trait Loci
MH  - Tendinopathy/*genetics
MH  - Tissue Inhibitor of Metalloproteinase-2/*genetics
OTO - NOTNLM
OT  - Achilles tendinopathy susceptibility
OT  - Genetic association studies
OT  - MMP3
OT  - Single nucleotide polymorphism
OT  - TIMP2
EDAT- 2019/06/19 06:00
MHDA- 2019/12/20 06:00
CRDT- 2019/06/19 06:00
PHST- 2018/12/27 00:00 [received]
PHST- 2019/04/13 00:00 [revised]
PHST- 2019/05/30 00:00 [accepted]
PHST- 2019/06/19 06:00 [pubmed]
PHST- 2019/12/20 06:00 [medline]
PHST- 2019/06/19 06:00 [entrez]
AID - S1440-2440(18)31312-4 [pii]
AID - 10.1016/j.jsams.2019.05.021 [doi]
PST - ppublish
SO  - J Sci Med Sport. 2019 Oct;22(10):1074-1078. doi: 10.1016/j.jsams.2019.05.021. 
      Epub 2019 Jun 7.