Collagen genes and exercise-associated muscle cramping

Clin J Sport Med. 2013 Jan;23(1):64-9. doi: 10.1097/JSM.0b013e3182686aa7.


Objective: The authors hypothesized that variants within genes, such as COL5A1, COL3A1, COL6A1, and COL12A1, that code for connective tissue components of the musculoskeletal system may modulate susceptibility to exercise-associated muscle cramping (EAMC). Specifically, the aim of this study was to investigate if the COL5A1 rs12722 (C/T), COL3A1 rs1800255 (G/A), COL6A1 rs35796750 (T/C), and COL12A1 rs970547 (A/G) polymorphisms are associated with a history of EAMC.

Design: Retrospective genetic case-control association study.

Setting: Participants were recruited at triathlon and ultra-marathon events and were asked to report physical activity, medical history, and cramping history.

Participants: One hundred sixteen participants with self-reported history of EAMC within the past 12 months before an ultra-endurance event were included as cases in this study (EAMC group). One hundred fifty participants with no self-reported history of previous (lifelong) EAMC were included as controls (NON group).

Interventions: All participants were genotyped for the selected variants.

Main outcome measures: Differences in genotype frequency distributions, for COL5A1 rs12722, COL3A1 rs1800255, COL6A1 rs35796750, and COL12A1 rs970547, among the cases and controls.

Results: The COL5A1 CC genotype was significantly overrepresented (P = 0.031) among the NON group (21.8%) when compared with the EAMC group (11.1%). No significant genotype differences were found for the COL3A1 (P = 0.828), COL6A1 (P = 0.300), or COL12A1 (P = 0.120) genotypes between the EAMC and NON groups.

Conclusions: This study identified, for the first time, the COL5A1 gene as a potential marker for a history of EAMC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Collagen Type III / genetics*
  • Collagen Type V / genetics*
  • Collagen Type VI / genetics*
  • Collagen Type XII / genetics*
  • Exercise / physiology*
  • Genetic Association Studies
  • Genetic Markers
  • Genotype
  • Genotyping Techniques
  • Humans
  • Logistic Models
  • Middle Aged
  • Muscle Cramp / etiology
  • Muscle Cramp / genetics*
  • Polymorphism, Single Nucleotide*
  • Retrospective Studies
  • Risk Factors
  • Self Report


  • COL12A1 protein, human
  • COL3A1 protein, human
  • COL5A1 protein, human
  • Col6a1 protein, human
  • Collagen Type III
  • Collagen Type V
  • Collagen Type VI
  • Collagen Type XII
  • Genetic Markers