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Updated: Jan 3, 2026

Author Spotlight: Integrating Mechanical and Biological Analysis in Tendinopathy Research
Published on: March 1, 2024
Variability within the human iNOS gene and Achilles tendon injuries: Evidence for a heterozygous advantage effect
Charlotte Brookes1, William J Ribbans1, Louis Y El Khoury2
1Faculty of Health and Society, University of Northampton, UK.
Objectives:
The aim of this case control genetic association study was to explore whether two variants within the inducible nitric oxide synthase (iNOS) gene, rs2779249 (C/A) and rs2248814 (A/G), influenced the risk of Achilles tendinopathy in a British population.
Design:
Candidate gene, case control association study.
Method:
We recruited 145 individuals diagnosed with Achilles tendon pathology and 132 asymptomatic controls. All participants were genotyped for the iNOS variants using qPCR and significant associations were discovered using a combination of Chi squared and ANOVA type analysis.
Results:
The CA genotype of the iNOS rs2779249 variant was protective and conformed to a heterozygous advantage model of inheritance as it was overrepresented in the control participants (p=0.009). In sex specific analysis the protective association persisted in male participants (p=0.016) but not in females. Unlike the rs2779249 variant, the rs2248814 variant was not associated with Achilles tendinopathy or Achilles tendon rupture.
Conclusion:
The rs2779249 CA genotype within the human iNOS gene appears to protect individuals from Achilles tendinopathy. This study further supports a genetic contribution to modifying the risk of Achilles tendon problems. The study also infers an important role for nitric oxide in tendon healing and/or degradation.
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