Female Athletes Genetically Susceptible to Fatigue Fracture Are Resistant to Muscle Injury: Potential Role of COL1A1 Variant

Eri Miyamoto-Mikami, Hiroshi Kumagai, Kumpei Tanisawa, Yuki Taga, Kosuke Hirata, Naoki Kikuchi, Nobuhiro Kamiya, Ryoko Kawakami, Taishi Midorikawa, Takuji Kawamura, Ryo Kakigi, Toshiharu Natsume, Hirofumi Zempo, Koya Suzuki, Yoshimitsu Kohmura, Kazunori Mizuno, Suguru Torii, Shizuo Sakamoto, Koichiro Oka, Mitsuru HiguchiHisashi Naito, Naokazu Miyamoto, Noriyuki Fuku*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Purpose We aimed to investigate the hypothesis that type I collagen plays a role in increasing bone mineral density (BMD) and muscle stiffness, leading to low and high risks of fatigue fracture and muscle injury, respectively, in athletes. As a potential mechanism, we focused on the effect of the type I collagen alpha 1 chain gene (COL1A1) variant associated with transcriptional activity on bone and skeletal muscle properties. Methods The association between COL1A1 rs1107946 and fatigue fracture/muscle injury was evaluated in Japanese athletes. Effects of the polymorphism on tissue properties (BMD and muscle stiffness) and type I collagen α1/α2 chain ratios in muscles were examined in Japanese nonathletes. Results The C-allele carrier frequency was greater in female athletes with fatigue fracture than in those without (odds ratio = 2.44, 95% confidence interval [CI] = 1.17-5.77) and lower in female athletes with muscle injury than in those without (odds ratio = 0.46, 95% CI = 0.24-0.91). Prospective validation analysis confirmed that in female athletes, muscle injury was less frequent in C-allele carriers than in AA genotype carriers (multivariable-adjusted hazard ratio = 0.27, 95% CI = 0.08-0.96). Among female nonathletes, the C-allele of rs1107946 was associated with lower BMD and lower muscle stiffness. Muscle biopsy revealed that C-allele carriers tended to have a larger type I collagen α1/α2 chain ratio than AA genotype carriers (2.24 vs 2.05, P = 0.056), suggesting a higher proportion of type I collagen α1 homotrimers. Conclusion The COL1A1 rs1107946 polymorphism exerts antagonistic effects on fatigue fracture and muscle injury among female athletes by altering the properties of these tissues, potentially owing to increased levels of type I collagen α1 chain homotrimers.

Original languageEnglish
Pages (from-to)1855-1864
Number of pages10
JournalMedicine and Science in Sports and Exercise
Issue number9
Publication statusPublished - 2021


  • BMD

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation


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