The <i>COL5A1</i> gene and musculoskeletal soft-tissue injuries

Abstract

Background. It has been shown that there is an association between various genetic variants and Achilles tendon injuries as well as anterior cruciate ligament (ACL) ruptures. Among other variants the BstUI restriction fragment length polymorphism (RFLP) within the COL5A1 gene has been shown to be over-represented in asymptomatic participants when compared with those with chronic Achilles tendinopathy, and in asymptomatic female participants when compared with those with ACL ruptures. The male asymptomatic control participants in the ACL study, which were 10 years younger than previously investigated cohorts, had a distinctly different genotype frequency. Aim. The aim of this study was therefore to determine whether the distribution of the COL5A1 BstUI RFLP in the combined asymptomatic participants without any known history of tendon injuries is age dependent, particularly among males. Results. When the 265 male asymptomatic participants from all studies were pooled and divided into age-group tertiles, there was a significant linear increase in the CC genotype frequency (p=0.032) among the male age groups, with the youngest group having the lowest frequency (CC genotype frequency, 13%) and the oldest group having the highest (CC genotype frequency, 27%) frequency. There was however a similar CC genotype content in all three female (N=231) age groups (CC genotype frequency, 24 - 27%; p=0.795). Conclusion. The practical implication is that the selection of asymptomatic groups is of critical importance when future studies of this nature are designed. Future research investigating this genetic variant as a risk factor for soft-tissue injuries should consider these findings when selecting asymptomatic participants.

The Variants Within the COL5A1 Gene are Associated with Reduced Risk of Anterior Cruciate Ligament Injury in Skiers

“…The functional COL5A1 Sp1 binding site polymorphism - BstUI RFLP, known also as: rs 12722, C/T is associated with a number of sport injuries. This polymorphism was detected in a physically active Caucasian population in South Africa ( Posthumus et al, 2010 ).…”

Are commercial genetic injury tests premature?

“…This highlights the possibility that there is a subset of polymorphisms that protect individuals from a specific injury and that matching controls with cases for all possible confounding factors, such as exposure to the same sport, level of training, among others, is an important consideration in future research. 46 This is currently a limitation in the GWAS studies published to date since these subsets of polymorphisms would not be identified in GWAS where the controls represent the general population. 47 In addition to the CC genotype, the TT genotype was also independently associated with reduced risk of Achilles tendinopathy in the Australian (Aus) population (Figure 2).…”

“… 42,43,45 Interestingly, when compared to the general population the CC genotype was over‐represented in the asymptomatic physically active controls with no history of Achilles tendon injuries, while the CC genotype of the Achilles tendinopathy group was similar to the general population. This highlights the possibility that there is a subset of polymorphisms that protect individuals from a specific injury and that matching controls with cases for all possible confounding factors, such as exposure to the same sport, level of training, among others, is an important consideration in future research 46 . This is currently a limitation in the GWAS studies published to date since these subsets of polymorphisms would not be identified in GWAS where the controls represent the general population 47 …”