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Functional polymorphisms within the inflammatory pathway regulate expression of extracellular matrix components in a genetic risk dependent model for anterior cruciate ligament injuries.
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2019 (Engelska)Ingår i: Journal of Science and Medicine in Sport, ISSN 1440-2440, E-ISSN 1878-1861, Vol. 22, nr 11, s. 1219-1225Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

OBJECTIVES: To investigate the functional effect of genetic polymorphisms of the inflammatory pathway on structural extracellular matrix components (ECM) and the susceptibility to an anterior cruciate ligament (ACL) injury.

DESIGN: Laboratory study, case-control study.

METHODS: Eight healthy participants were genotyped for interleukin (IL)1B rs16944 C>T and IL6 rs1800795 G>C and classified into genetic risk profile groups. Differences in type I collagen (COL1A1), type V collagen (COL5A1), biglycan (BGN) and decorin (DCN) gene expression were measured in fibroblasts either unstimulated or following IL-1β, IL-6 or tumor necrosis factor (TNF)-α treatment. Moreover, a genetic association study was conducted in: (i) a Swedish cohort comprised of 116 asymptomatic controls (CON) and 79 ACL ruptures and (ii) a South African cohort of 100 CONs and 98 ACLs. Participants were genotyped for COL5A1 rs12722 C>T, IL1B rs16944 C>T, IL6 rs1800795 G>C and IL6R rs2228145 G>C.

RESULTS: IL1B high-risk fibroblasts had decreased BGN (p=0.020) and COL5A1 (p=0.012) levels after IL-1β stimulation and expressed less COL5A1 (p=0.042) following TNF-α treatment. Similarly, unstimulated IL6 high-risk fibroblasts had lower COL5A1 (p=0.012) levels than IL6 low-risk fibroblasts. In the genetic association study, the COL5A1-IL1B-IL6 T-C-G (p=0.034, Haplo-score 2.1) and the COL5A1-IL1B-IL6R T-C-A (p=0.044, Haplo-score: 2.0) combinations were associated with an increased susceptibility to ACL injury in the Swedish cohort when only male participants were evaluated.

CONCLUSIONS: This study shows that polymorphisms within genes of the inflammatory pathway modulate the expression of structural and fibril-associated ECM components in a genetic risk depended manner, contributing to an increased susceptibility to ACL injuries.

Ort, förlag, år, upplaga, sidor
Elsevier, 2019. Vol. 22, nr 11, s. 1219-1225
Nyckelord [en]
Anterior cruciate ligament injury, Extracellular matrix, Genetics, Personalized medicine, Polymorphisms
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Identifikatorer
URN: urn:nbn:se:umu:diva-163874DOI: 10.1016/j.jsams.2019.07.012PubMedID: 31395468Scopus ID: 2-s2.0-85072364464OAI: oai:DiVA.org:umu-163874DiVA, id: diva2:1358049
Tillgänglig från: 2019-10-07 Skapad: 2019-10-07 Senast uppdaterad: 2019-10-08Bibliografiskt granskad

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Häger, CharlotteNilsson, Kjell G

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Avdelningen för fysioterapiInstitutionen för kirurgisk och perioperativ vetenskap
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Journal of Science and Medicine in Sport
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