bd95074e0f476e29b5e5a066a5bd7ac5 pmc_9858943.pdf 124699407ce5b4e947db1bd2821f7c27f406ea63 pmc_9858943.pdf 119537cd161537dc7347b9a483719556eae887665421d1a3977da0bd99faf455 pmc_9858943.pdf Title: Sex Differences in the Association between Risk of Anterior Cruciate Ligament Rupture and COL5A1 Polymorphisms in Elite Footballers Subject: Background: Single-nucleotide polymorphisms (SNPs) in collagen genes are predisposing factors for anterior cruciate ligament (ACL) rupture. Although these events are more frequent in females, the sex-specific risk of reported SNPs has not been evaluated. Purpose: We aimed to assess the sex-specific risk of historic non-contact ACL rupture considering candidate SNPs in genes previously associated with muscle, tendon, ligament and ACL injury in elite footballers. Study Design: This was a cohort genetic association study. Methods: Forty-six (twenty-four females) footballers playing for the first team of FC Barcelona (Spain) during the 2020–21 season were included in the study. We evaluated the association between a history of non-contact ACL rupture before July 2022 and 108 selected SNPs, stratified by sex. SNPs with nominally significant associations in one sex were then tested for their interactions with sex on ACL. Results: Seven female (29%) and one male (4%) participants had experienced non-contact ACL rupture during their professional football career before the last date of observation. We found a significant association between the rs13946 C/C genotype and ACL injury in women footballers (p = 0.017). No significant associations were found in male footballers. The interaction between rs13946 and sex was significant (p = 0.027). We found that the C-allele of rs13946 was exclusive to one haplotype of five SNPs spanning COL5A1. Conclusions: The present study suggests the role of SNPs in genes encoding for collagens as female risk factors for ACL injury in football players. Clinical Relevance: The genetic profiling of athletes at high risk of ACL rupture can contribute to sex-specific strategies for injury prevention in footballers. Keywords: anterior cruciate ligament; injury; single-nucleotide polymorphisms; female; team sport; football; collagen; COL5A1; rs13946; rs12722; sex differences Author: Gil Rodas, Alejandro Cáceres, Eva Ferrer, Laura Balagué-Dobón, Lourdes Osaba, Alejandro Lucia and Juan R. González Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Jan 6 10:24:34 2023 CET ModDate: Fri Jan 6 10:45:49 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 9 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 508827 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SXQPWE+VnURWPalladioL Type 1 Custom yes yes no 10 0 OMKKDT+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 AJIPKR+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 ILKUIE+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 ZZTQUO+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 KONDUX+EuphemiaUCAS-Bold Type 1C WinAnsi yes yes no 46 0 HIZBRM+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 NUUXUW+VnURWPalladioL-Italic Type 1 Custom yes yes no 74 0 PIDIHI+URWPalladioL-BoldItal Type 1 Custom yes yes no 81 0 PUIIPU+PalatinoLinotype-Italic TrueType WinAnsi yes yes yes 91 0 CQWIPU+PalatinoLinotype-Roman TrueType WinAnsi yes yes yes 95 0 WUWDJG+PalatinoLinotype-Bold TrueType WinAnsi yes yes yes 99 0 CKBPVA+EURM10 Type 1 Builtin yes yes no 107 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-11-08 02:28:36 CET RepresentationInformation: pmc_9858943.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-02-02 03:40:02 CET Size: 508827 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 237 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Children: Item: Title: Participants Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Ethics Statement Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Genotyping Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Info: Title: Sex Differences in the Association between Risk of Anterior Cruciate Ligament Rupture and COL5A1 Polymorphisms in Elite Footballers Author: Gil Rodas, Alejandro Cáceres, Eva Ferrer, Laura Balagué-Dobón, Lourdes Osaba, Alejandro Lucia and Juan R. González Subject: Background: Single-nucleotide polymorphisms (SNPs) in collagen genes are predisposing factors for anterior cruciate ligament (ACL) rupture. Although these events are more frequent in females, the sex-specific risk of reported SNPs has not been evaluated. Purpose: We aimed to assess the sex-specific risk of historic non-contact ACL rupture considering candidate SNPs in genes previously associated with muscle, tendon, ligament and ACL injury in elite footballers. Study Design: This was a cohort genetic association study. Methods: Forty-six (twenty-four females) footballers playing for the first team of FC Barcelona (Spain) during the 2020 21 season were included in the study. We evaluated the association between a history of non-contact ACL rupture before July 2022 and 108 selected SNPs, stratified by sex. SNPs with nominally significant associations in one sex were then tested for their interactions with sex on ACL. Results: Seven female (29%) and one male (4%) participants had experienced non-contact ACL rupture during their professional football career before the last date of observation. We found a significant association between the rs13946 C/C genotype and ACL injury in women footballers (p = 0.017). No significant associations were found in male footballers. The interaction between rs13946 and sex was significant (p = 0.027). We found that the C-allele of rs13946 was exclusive to one haplotype of five SNPs spanning COL5A1. Conclusions: The present study suggests the role of SNPs in genes encoding for collagens as female risk factors for ACL injury in football players. Clinical Relevance: The genetic profiling of athletes at high risk of ACL rupture can contribute to sex-specific strategies for injury prevention in footballers. Keywords: anterior cruciate ligament; injury; single-nucleotide polymorphisms; female; team sport; football; collagen; COL5A1; rs13946; rs12722; sex differences Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Jan 06 10:24:34 CET 2023 ModDate: Fri Jan 06 10:45:49 CET 2023 ID: 0xd22de9a9da6ee4582d95d6c393746cf2, 0xd22de9a9da6ee4582d95d6c393746cf2 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: PIDIHI+URWPalladioL-BoldItal FontSubset: true FirstChar: 61 LastChar: 112 FontDescriptor: FontName: PIDIHI+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: AJIPKR+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: AJIPKR+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ILKUIE+URWPalladioL-Ital FontSubset: true FirstChar: 46 LastChar: 121 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