Available online at www.sciencedirect.com
Journal of Science and Medicine in Sport 13 (2010) 630–632
A functional variant within the MMP3 gene does not associate with
human range of motion
Michael Posthumusa,∗, Stuart M. Raleigha, William J. Ribbansa,
Martin P. Schwellnusb, Malcolm Collinsb,c
aThe Division of Health and Life Sciences, University of Northampton, Northampton, United Kingdom
bUCT/MRC Research Unit for Exercise Science and Sports Medicine of the Department of Human Biology,
Faculty of Health Sciences, University of Cape Town, South Africa
cSouth African Medical Research Council, Cape Town, South Africa
Received 26 October 2009; received in revised form 18 January 2010; accepted 28 January 2010
A recent heritability study has demonstrated that human range of motion (ROM) has a substantial genetic component. Furthermore, the
COL5A1 BstUI RFLP has now been identified as the first gene variant to be associated with human ROM. Interestingly, this variant is known
to interact with a functional variant within the MMP3 gene (rs679620) to increase risk of Achilles tendinopathy. We sought to determine
whether the MMP3 rs679620 variant was associated with ROM both as a single marker and as an interacting marker with the COL5A1 BstUI
RFLP. One hundred and twenty one participants were included in this study. All participants were genotyped for the MMP3 rs679620 variant,
and performed passive straight leg raise (SLR) and sit and reach (SR) measurements. There were no significant differences in left leg SLR
(L-SLR), right leg SLR (R-SLR), or SR measurements between the genotype groups (L-SLR, P=0.494; R-SLR, P=0.435; SR, P=0.266).
Furthermore, there was no evidence of an interaction between the COL5A1 BstUI RFLP and the MMP3 rs679620 variant. Our study suggests
that the MMP3 rs679620 variant does not associate with passive ROM.
© 2010 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.
Keywords: Stretching; Flexibility; Matrix metalloproteinase; Association; Polymorphism; Genotype
Musculotendinous range of motion (ROM), also referred
extent of movement in a specific plane that is achievable in
one joint or a group of joints without sustaining an injury.1
an intrinsic risk factor for soft tissue injuries. Although con-
have shown that both increased and decreased ROM may be
associated with an increased risk of injury.2,3Therefore, the
clinical measurement of ROM has relevance, and the fac-
tors that determine ROM are important in understanding risk
factors that may be associated with soft tissue injuries.
E-mail address: firstname.lastname@example.org (M. Posthumus).
Although various factors have been shown to influence
ROM, a heritability study has determined that the predom-
inant factor (67%) is genetics.4Despite this fact, to our
that has been associated with ROM.5Collins et al.5reported
that the COL5A1 BstUI restriction fragment length poly-
morphism (RFLP) was associated with two clinical ROM
the sit and reach (SR) test. It is unlikely that this is the only
which code for proteins with regulatory roles in maintaining
the extracellular matrix (ECM) homeostasis.
The COL5A1 BstUI RFLP has also recently been associ-
ated with Achilles tendinopathy, a common musculoskeletal
Metalloproteinase 3, a key regulator of the ECM, which is
1440-2440/$ – see front matter © 2010 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.
M. Posthumus et al. / Journal of Science and Medicine in Sport 13 (2010) 630–632
Left and right leg passive straight leg raise (SLR) and sit and reach (SR) measurements of all participants in the study (ALL), as well as the AA, AG or GG
MMP3 rs679620 genotype groups.
MMP3 rs679620 variant
AA genotype (N=27) AG genotype (N=47)GG genotype (N=31)
Right SLR (◦)
Left SLR (◦)
Values are expressed as mean±standard deviation. Number of participants (N) is in parentheses.
aCo-varied for age, weight and gender.
and other matrix proteins,8has also been shown to asso-
ciate with Achilles tendinopathy.9Specifically, the MMP3
rs679620 GG genotype was significantly over-represented
within individuals with Achilles tendinopathy. In addition,
Raleigh et al.9also reported a significant interaction between
the MMP3 rs679620 variant and the COL5A1 BstUI RFLP
and risk of Achilles tendinopathy.
The aim of this study was therefore to investigate whether
the MMP3 rs679620 variant influences passive ROM mea-
surements. A secondary aim was to investigate whether
interaction exists between ROM measurements, the MMP3
rs679620 variant and the COL5A1 BstUI RFLP.
One hundred and twenty one participants were recruited
for this study at the Sport Science Institute of South Africa
in Cape Town, as previously described.6,7,9The physical
characteristics of all participants, as well as the respective
MMP3 rs679620 genotype groups are detailed in the addi-
consent and completed a self-reported flexibility training
committees of the faculty of Health Sciences within the Uni-
versity of Cape Town, South Africa and the University of
Each participant completed ROM measurements, includ-
ing a passive straight leg raise (SLR) measurement on each
leg and a sit and reach (SR) measurement, as previously
ments showed high consistency (Rs>0.90).5
Participants’ genotypic data for both MMP3 rs679620
and the COL5A1 BstUI RFLP were collected as part of
our earlier studies and have been previously described.6,9
A one-way analysis of variance (ANOVA) was used to
determine any significant difference between the character-
istics of the genotype groups. A chi-squared (χ2) test was
used to analyse any differences in gender and the domi-
nant hand of participants. P-values for the differences in
for age, weight and gender. Significance was accepted at
There were no significant differences in left leg SLR,
right leg SLR, or SR measurements between the genotype
groups before (L-SLR, P=0.220; R-SLR, P=0.218; SR,
P=0.149) and after (L-SLR, P=0.494; R-SLR, P=0.435;
SR, P=0.266) the P-values were co-varied for age, weight
and gender (Table 1). In addition, there was no evidence
of interaction between ROM and the MMP3 rs679620 and
COL5A1 BstUI RFLP genotype pairs (see additional mate-
rial; Table S2).
We report no significant association between the MMP3
rs679620 variant and ROM measurements. Furthermore, we
found no interaction between the MMP3 rs679620 variant,
the COL5A1 BstUI RFLP and ROM measurements. These
data suggests that the MMP3 gene does not associate with
ROM measurements, individually, or with COL5A1. A pre-
viously published report has shown that the COL5A1 BstUI
RFLP associates with ROM measurements. Moreover, the
predominant (64%) factor in the variance in lumbar ROM
during flexion has been shown to be attributed to genetic
influences (heritability).4Although the variance within the
encouraged to explore the influences of additional sequence
variants within genes which regulate the ECM on ROM phe-
ated with Achilles tendon injuries.5The link between ROM
and Achilles tendon injuries remains a contentious issue,6,7
however, it remains likely that genetic variants may affect
the risk of Achilles tendon injuries by contributing to either
an increased or a decreased ROM. The lack of associa-
tion we report in this study may indirectly suggest that the
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M. Posthumus et al. / Journal of Science and Medicine in Sport 13 (2010) 630–632
injuries through mechanisms independent of ROM. Further
aetiology remains unknown.
Although a larger sample size would have increased the
power of this study, it is important to mention that variability
by genetic sequence variation.5A limitation of this study
was that flexibility training was not well documented in all
the subjects. Although there were no significant differences
between flexibility training and genotype (Table S1), the rel-
atively few number of individuals with complete data for this
variable prevented further analysis.
Understanding the genetic contribution of ROM has
important clinical applications. Risk stratification and future
injury prevention models require the discovery of specific
genetic factors which influence ROM. It is therefore encour-
aged that researchers explore the influence of additional
sequence variant on ROM phenotypes.
This study was supported in part by funds from the
National Research Foundation (NRF) of South Africa, The
University of Cape Town, The University of Northampton
and the South African Medical Research Council (MRC).
Author MP was supported by a research fellowship from the
The authors would like to thank Dr GG Mokone for assis-
tance in the recruitment and the phenotypic data collection
Appendix A. Supplementary data
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