rs12722
badMag 4.5This is a 3 prime utr variant variant in the COL5A1 gene.
Key Literature Trait Associations
Achilles Tendon Injury Risk
rs12722 in the 3'-UTR of COL5A1 affects the stability and secondary structure of the mRNA, altering type V collagen production. Type V collagen is a minor but critical component of collagen fibrils in tendons, where it regulates fibril diameter. The T allele is associated with altered fibril assembly and reduced tendon mechanical strength, increasing susceptibility to Achilles tendinopathy and rupture, particularly in physically active populations.
Musculoskeletal soft tissue injury
rs12722 in COL5A1 is the most extensively studied genetic variant for general musculoskeletal soft tissue injury (MSTI) susceptibility, encompassing tendon and ligament pathologies. The 2018 Lv et al. meta-analysis (9 studies, 2,550 participants) found TT genotype associated with OR 1.58 for MSTI overall, with strong evidence in Caucasians. A 2022 meta-analysis expanding to 21 studies confirmed this association. However, a 2023 critical review by the original research group cautioned that the evidence base remains insufficient for standalone commercial genetic testing of injury risk.
Anterior cruciate ligament injury
The rs12722 T allele in COL5A1 has been associated with elevated ACL injury susceptibility, particularly in Caucasian populations. The 2018 meta-analysis by Lv et al. identified a significant association of TT genotype with ACL injuries as a specific subgroup of musculoskeletal soft tissue injuries. A 2022 expanded meta-analysis of 21 studies confirmed this, finding the association primarily in ligament injury subtypes and Caucasian populations. The effect appears weaker than for Achilles tendinopathy and has not been consistently replicated in all populations or age groups.
Joint laxity
The CC genotype of rs12722 has been associated with decreased active and passive knee hyperextension (reduced joint laxity) when combined with other collagen gene variants, consistent with the role of COL5A1 in regulating collagen fibril architecture and tissue stiffness. This finding was reported in a small cross-sectional study (n=106) and requires replication. The functional direction aligns with the protective effect of the CC genotype seen in tendon injury studies.
▶ClinVar annotation
Ehlers-Danlos syndrome type 7A; Fibromuscular dysplasia, multifocal; not provided; Ehlers-Danlos syndrome, classic type, 1
View on ClinVar →▶Research that mentions this SNP (4)
▶Association of the matrix metalloproteinase 3 (MMP3) single nucleotide polymorphisms with tendinopathies: case-control study in high-level athletesCase reportNina Briški et al.(2021)· International Orthopaedics
This is a Turkish-language personalized nutrigenetics and epigenetics coaching report for individual Mehmet Efe Yildirim (Report No. 1332, dated 2023-11-21). The report analyzes the individual's genetic polymorphisms related to nutritional metabolism, food sensitivities, detoxification pathways, and other health-related traits, providing personalized dietary and lifestyle recommendations based on cited scientific literature. This is a direct-to-consumer genetic test report, not a peer-reviewed research study.
▶Exploring new genetic variants within COL5A1 intron 4‐exon 5 region and TGF‐β family with risk of anterior cruciate ligament rupturesReviewN=9,720Mary‐Jessica N. Laguette et al.(2020)· Journal of Orthopaedic Research
This systematic review analyzed 24 studies examining 31 genes and 62 genetic variants associated with anterior cruciate ligament rupture (ACLR). Key findings show mixed evidence for collagen variants: COL1A1 rs1800012 showed protective association in European ancestry populations (OR=2.8, p=0.040), while COL1A2 rs42524 and rs2621215 conferred increased risk (OR=5.73 and 4.29 respectively). VEGFA polymorphisms rs2010963 and rs699947 showed conflicting associations across studies, and most major variants in IL6, IL1B, MMP genes, and inflammatory markers showed no consistent associations with ACLR across populations, highlighting the need for gender and ancestry-stratified analyses.
▶Investigation of variants within the COL27A1 and TNC genes and Achilles tendinopathy in two populationsAssociationN=890Colleen J. Saunders et al.(2013)· Journal of Orthopaedic Research
PhD dissertation examining genetic variants in collagen genes (COL22A1, COL27A1, COL11A1) and anterior cruciate ligament injury risk in Polish athletes. Paper 1 is a systematic review of genetic determinants of ACL rupture. Papers 2 and 3 are case-control association studies finding no significant associations between SNPs rs11784270/rs6577958 (COL22A1), rs946053 (COL27A1), and rs3753841 (COL11A1) and non-contact ACL injury risk in Polish athletes.
▶Bilateral consecutive rupture of the quadriceps tendon in a man with BstUI polymorphism of the COL5A1 geneCase reportUmile Giuseppe Longo et al.(2010)· Knee Surgery, Sports Traumatology, Arthroscopy
A case report of a 54-year-old man with bilateral consecutive ruptures of the quadriceps tendon who was found to carry the BstUI polymorphism (rs12722) of the COL5A1 gene. Histopathological analysis revealed profound degenerative changes not only at the rupture sites but also in macroscopically intact tendon portions. The authors propose COL5A1 rs12722 as a candidate genetic factor associated with quadriceps tendon rupture susceptibility.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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