The COL5A1 genotype is associated with range of motion measurements M. Collins 1,2 , G. G. Mokone 1 , A. V. September 1 , L. van der Merwe 3,4 , M. P. Schwellnus 1 1 UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa, 2 UCT/MRC Research Unit for Exercise Science and Sports Medicine, South African Medical Research Council, Cape Town, South Africa, 3 Biostatistics Unit, South African Medical Research Council, Cape Town, South Africa, 4 Department of Statistics, University of Western Cape, Cape Town, South Africa Corresponding author: Prof. Malcom Collins, UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, PO Box 115, Newlands, 7725, South Africa. Tel: 127 21 650 4574, Fax: 127 21 686 7530, E-mail: malcolm.collins@uct.ac.za Accepted for publication 28 December 2008 There is an interest in identifying the intrinsic risk factors, including altered musculotendinous flexibility, that may be associated with musculotendinous injuries. We have recently shown that a sequence variant, namely the BstUI restriction fragment length polymorphism (RFLP), within the COL5A1 gene is associated with chronic Achilles tendino- pathy. Mutations within COL5A1 have been implicated in Ehlers Danlos syndrome, a condition that is characterized by joint hypermobility. The aim of this study was to investigate the association of sequence variants within COL5A1 and musculotendinous range of motion (ROM). The sit and reach (SR) and the passive straight leg raise (SLR) were measured on 119 Caucasian subjects with either a past, current or no history of Achilles tendon injuries. The subjects were genotyped for four sequence variants within the 3 0 -UTR of the COL5A1 gene. Gender (P 5 0.016), age (P 5 0.011) and the BstUI RFLP (P 5 0.010) jointly con- tributed significantly to the optimal SLR model which accounted for 19.3% of the variance. The factors contribut- ing significantly to SR, which accounted for 28.8% of the variance, were weight (P 5 0.004), age (Po0.001) and the BstUI RFLP (P 5 0.001). These data suggest that the COL5A1 BstUI RFLP is independently associated with lower limb ROM within the cohort investigated in this study. Musculotendinous injuries continue to make up a large proportion of the injuries reported by both athletes participating in different sports (Arnason et al., 2004; Dadebo et al., 2004) and military recruits undergoing basic training (Amako et al., 2003). Altered musculotendinous flexibility, which can be defined as ‘‘the ability to move a joint through its complete range of motion’’ (ROM) (Whaley, 2006), has been cited as an intrinsic risk factor for these injuries (Knapik et al., 1991, 1992; Wang et al., 1993; Krivickas & Feinberg, 1996). Some reviewers have suggested that reduced flexibility may not be strongly associated with an increased injury risk (Pope et al., 2000; Yeung & Yeung, 2001; Thacker et al., 2004). However, more recent prospective studies have shown that reduced flexibility is associated with an increased risk of muscle strain injury (Amako et al., 2003; Witvrouw et al., 2003; Arnason et al., 2004), particularly, if there was no history of a previous injury (Witvrouw et al., 2003). Furthermore, general- ized joint laxity has also been associated with an increased risk of injury if athletes or military recruits are followed for a season or a training period (Krivickas & Feinberg, 1996; Jones & Knapik, 1999). Possible reasons for the current controversy relating injuries to reduced flexibility have recently been reviewed (Witvrouw et al., 2004). Despite this controversy, it is still common practice that athletes stretch their muscle-tendon units (MTU), before, during or after physical activity in order to increase joint ROM (Johnston et al., 2003; Dadebo et al., 2004; Witvrouw et al., 2004; Verrall et al., 2005). Although flexibility can be improved through regular stretching, it could at least in part also be determined genetically (Hakim et al., 2004). In sup- port of this, there is a group of rare heritable disorders of connective tissue (HDCTs) with a uni- fying characteristic of generalized joint hypermobi- lity (Grahame, 1999; Hakim & Grahame, 2003). It has been suggested that benign joint hypermobility syndrome (BJHS) is also an inherited condition (Grahame, 1999; Zweers et al., 2005). In addition, a genetic epidemiology study consisting of 483 mono- zygotic and 472 dizygotic female twin pairs reported that there is a strong genetic component to self- reported joint hypermobility (Hakim et al., 2004). Scand J Med Sci Sports 2009: 19: 803–810 & 2009 John Wiley & Sons A/S doi: 10.1111/j.1600-0838.2009.00915.x 803