A Polymorphism in a Functional Region of the COL5A1 Gene: Association With Ultraendurance-Running Performance and Joint Range of Motion

Purpose: Endurance-running performance and joint range of motion (ROM) are both multifactorial phenotypes. A single-nucleotide polymorphism, rs172722 (C/T), in the COL5A1 3'-untranslated region (UTR) was shown to independently associate with both phenotypes. Two major functional forms of the COL5A1 3'-UTR have been identified and differ by 7 tightly linked polymorphisms that include rs12722 and a short tandem-repeat polymorphism (STRP rs71746744, -/AGGG). It has been proposed that STRP rs71746744 plays a role in the predicted secondary structures and mRNA stability of the 2 major forms of the COL5A1 3'-UTR, therefore implying a regulatory role. The aim of this study was to determine whether STRP rs71746744 is independently associated with running performance and prerace sit-and-reach range of motion (SR ROM) in a cohort of ultramarathon road runners. Methods: One hundred six (74 men and 32 women, age 22-67 y) white runners who participated in either the 2009 or 2011 Two Oceans 56-km ultramarathon were included in this cross-sectional study. Their SR ROM measurements, COL5A1 rs71746744 genotype, and overall race times were determined. Results: COL5A1 rs71746744 was independently associated with running performance (P = .024) and prerace SR ROM (P = .020). Moreover, the AGOG/AGOG genotype was significantly overrepresented in the fastest and inflexible athletes compared with those with either the -/AGOG or -/- genotype. Conclusions: These findings provide further evidence for a relationship between COL5A1, running performance, and SR ROM. Further studies are needed to investigate the effect of this variant on the mechanical properties of connective tissue.