title: Candidate gene approach identifies six SNPs in tenascin-C (TNC) associated with degenerative rotator cuff tears.
abstract: Evidence for a heritable predisposition to rotator cuff tears (RCTs) is growing. Unrelated Caucasian individuals with surgically diagnosed full thickness RCTs (cases) and elderly Caucasian controls with intact rotator cuffs were screened for differences at the candidate genes: TNC, Col5A1, TIMP-1, MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13. A first cohort (59 cases; 32 controls) was genotyped with the Sequenom MassARRAY iPLEX system. Of 142 SNPs within about 67-kbp of the TNC gene, 30 were tested for differences in proportions between cases and controls. A second, matched cohort (96 patients; 44 controls) was also genotyped for the same 30 SNPs, but with the KASP™ genotyping technology. Combining the two cohorts and after Bonferroni correction, six SNPs were significantly associated with RCT. Compared to controls, RCT patients showed a significantly higher rate of homozygosity at rs72758637, rs7021589, and rs1138545; a significantly higher rate of heterozygosity at rs10759753, rs3789870, and rs7035322 and a higher minor allele frequency at rs3789870. Rs1138545, a missense SNP in exon10 might be of biological significance because it varies the amino acid sequence close to the TNC-FNIII5 domain. The FNIII5 domain binds multiple growth factors and co-ligates with integrins during tendon healing. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:894-901, 2017.
authors.affiliation: Orthopedic Department of SMZOst Donauspital, Langobardenstrasse 122, A-1220, Vienna, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Kluger
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz1, A-1210, Vienna, Austria.|Institute of Biotechnology in Animal Production, Department IFA-Tulln, University of Natural Resources and Life Sciences, A-3430, Tulln, Austria.
authors.forename: Joerg
authors.initials: J
authors.lastname: Burgstaller
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz1, A-1210, Vienna, Austria.
authors.forename: Claus
authors.initials: C
authors.lastname: Vogl
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz1, A-1210, Vienna, Austria.|Institute of Biotechnology in Animal Production, Department IFA-Tulln, University of Natural Resources and Life Sciences, A-3430, Tulln, Austria.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Brem
authors.affiliation: Orthopedic Department of SMZOst Donauspital, Langobardenstrasse 122, A-1220, Vienna, Austria.|Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz1, A-1210, Vienna, Austria.
authors.forename: Michal
authors.initials: M
authors.lastname: Skultety
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz1, A-1210, Vienna, Austria.
authors.forename: Simone
authors.initials: S
authors.lastname: Mueller
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007592:Joint Diseases / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017006:Rotator Cuff / Q000473:pathology; D000070636:Rotator Cuff Injuries / Q000235:genetics*; D017422:Sequence Analysis, DNA; D019063:Tenascin / Q000235:genetics*; D044465:White People
chemical_list: D019063:Tenascin
keywords: FNIII5; genetic variant; rotator cuff tear; single nucleotid polymorphism; tenascin C