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Functional polymorp...
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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- Suijkerbuijk, Mathijs A. M. (författare)
- Univ Med Ctr Rotterdam, Dept Orthopaed Surg, Erasmus MC, Rotterdam, Netherlands
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- Ponzetti, Marco (författare)
- Univ Aquila, Dept Biotechnol & Appl Clin Sci, Laquila, Italy
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- Rahim, Masouda (författare)
- Univ Cape Town, Fac Hlth Sci, Dept Human Biol, Div Exercise Sci & Sports Med, Cape Town, South Africa
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- Posthumus, Michael (författare)
- Univ Cape Town, Fac Hlth Sci, Dept Human Biol, Div Exercise Sci & Sports Med, Cape Town, South Africa
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- Häger, Charlotte, 1962- (författare)
- Umeå universitet,Avdelningen för fysioterapi,Umea Univ, Dept Community Med & Rehabil, Umea, Sweden
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- Stattin, Evalena (författare)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
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- Nilsson, Kjell G (författare)
- Umeå universitet,Ortopedi,Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden
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- Teti, Anna (författare)
- Univ Aquila, Dept Biotechnol & Appl Clin Sci, Laquila, Italy
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- Meuffels, Duncan E. (författare)
- Univ Med Ctr Rotterdam, Dept Orthopaed Surg, Erasmus MC, Rotterdam, Netherlands
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- van der Eerden, Bram J. C. (författare)
- Univ Med Ctr Rotterdam, Dept Internal Med, Erasmus MC, Rotterdam, Netherlands
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- Collins, Malcolm (författare)
- Univ Cape Town, Fac Hlth Sci, Dept Human Biol, Div Exercise Sci & Sports Med, Cape Town, South Africa
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- September, Alison V. (författare)
- Univ Cape Town, Fac Hlth Sci, Dept Human Biol, Div Exercise Sci & Sports Med, Cape Town, South Africa
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(creator_code:org_t)
- Elsevier, 2019
- 2019
- Engelska.
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Ingår i: Journal of Science and Medicine in Sport. - : Elsevier. - 1440-2440 .- 1878-1861. ; 22:11, s. 1219-1225
- Relaterad länk:
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https://repub.eur.nl...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Sjukgymnastik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Physiotherapy (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Idrottsvetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Sport and Fitness Sciences (hsv//eng)
Nyckelord
- Anterior cruciate ligament injury
- Extracellular matrix
- Genetics
- Personalized medicine
- Polymorphisms
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- art (ämneskategori)
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Suijkerbuijk, Ma ...
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Ponzetti, Marco
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Rahim, Masouda
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Posthumus, Micha ...
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Häger, Charlotte ...
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Stattin, Evalena
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Nilsson, Kjell G
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Teti, Anna
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Meuffels, Duncan ...
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van der Eerden, ...
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Collins, Malcolm
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September, Aliso ...
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Umeå universitet
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