Polymorphic Variation within the
ADAMTS2, ADAMTS14, ADAMTS5, ADAM12, and TIMP2 Genes and the Risk of Achilles
Tendon Pathology: A Genetic Association Study
Khoury L, Posthumus M, Collins M, Handley CJ, Cook
J, Raleigh SM. J Sci Med Sport. 2013 Mar 11
Take Home Message: Achilles tendon
pathology is associated with variation within a gene (TIMP2) responsible for
inhibiting enzymes responsible for collagen degradation. Genetic pre-screening
of at-risk individuals may help guide individualized treatment strategies.
risk factors have recently been identified for Achilles tendon pathology, which
may allow for genetic screening and identification of at-risk patients and
could help guide clinical management of this injury. Specifically, previous
studies reviewed by SMR have shown that variants within genes
that encode for structural and regulatory proteins (such as Col5a1 and TNC) are associated with risk of Achilles
tendon pathology.  However, additional
genes encoding for enzymes that breakdown the extracellular matrix and their
inhibitors (such as the ADAM, ADAMTS, and TIMP family of proteins) have not yet
been evaluated.  Therefore, the purpose
of this study was to determine if variations within these genes are associated
with Achilles tendon pathology.  The
authors recruited 178 Caucasian participants diagnosed with Achilles tendon
pathology (59 Australian and 114 South African, 134 chronic and 39 acute ruptures)
and 248 asymptomatic Caucasian controls (152 Australian and 96 South African). DNA
was extracted from whole blood and all participants were genotyped for gene variants.  A significant association was found between a
TIMP2 variant and Achilles tendon pathology. 
Additionally, a significant interaction between an ADAMTS14 variant and
age of onset of Achilles tendon pathology was also identified. 
study introduces a TIMP2 variant as a significant risk factor for Achilles
tendon pathology.  TIMP2 is an inhibitor
of matrix metalloproteinases, which are enzymes responsible for extracellular
matrix degradation.  Increases in TIMP2
levels may disrupt extracellular matrix remodeling and overall tendon health.  The authors also identified a variant within
the ADAMTS14 gene that appeared to delay the onset of Achilles tendon pathology
in those affected.  ADAMTS14 is responsible
for cleavage of pro-collagen – an event which precedes the production of
collagen.  Results from this study
suggest a protective role may exist for this ADAMTS14 genotype.  Recently, much attention has been placed on
identifying genetic variations and understanding their association with tendon
pathology.  This study and previous
studies have concluded that genetic risk factors likely exist in tendon
pathology. Therefore, prescreening of individuals for these genetic variants
may help with clinical management. 
Specifically, individuals identified as genetically at risk may benefit
from individualized rehabilitation programs and more conservative return to
sport criteria. Despite these findings, Achilles tendon injury is likely due to
a complex interaction between both intrinsic (e.g., genetic) and extrinsic (e.g.,
repetitive mechanical stress) factors and therefore all factors should be
considered when treating patients.  

you think that individualized rehabilitation protocols could improve outcomes
in at risk patients?  Do you think genetic
testing should be implemented in college or professional sports? 
by: Katherine Reuther
by:  Stephen Thomas

El Khoury L, Posthumus M, Collins M, Handley CJ, Cook J, & Raleigh SM (2013). Polymorphic variation within the ADAMTS2, ADAMTS14, ADAMTS5, ADAM12 and TIMP2 genes and the risk of Achilles tendon pathology: A genetic association study. Journal of Science and Medicine in Sport PMID: 23491141