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The apoptosis pathway and the genetic predisposition to Achilles tendinopathy
Author(s) -
Nell EricaMari,
van der Merwe Lize,
Cook Jill,
Handley Christopher J.,
Collins Malcolm,
September Alison V.
Publication year - 2012
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22144
Subject(s) - tendinopathy , logistic regression , medicine , receiver operating characteristic , apoptosis , haplotype , bioinformatics , oncology , computational biology , gene , biology , genotype , genetics , pathology , tendon
Achilles tendinopathy (AT) is a degenerative condition for which several risk factors have been implicated including components of the inflammatory pathway. The aim was to assess functional variants within genes encoding components of the apoptosis signaling cascade and the effectiveness of a polygenic apoptosis profile to capture tendinopathy (TEN) risk. A total of 358 unaffected control (CON) participants [159 South Africa (SA CON) and 199 Australia (AUS CON)] and 166 affected AT (TEN) participants (87 SA TEN and 79 AUS TEN) were genotyped for four variants [ CASP8 (rs384129), CASP8 (rs1045485), NOS3 (rs1799983), and NOS2 (rs2779249)]. Logistic regression was used to derive risk models for AT. A receiver operator characteristic (ROC) curve was plotted to determine the effectiveness of a model to capture AT risk. This study indicates the independent association of CASP8 _rs1045485 and CASP8 _rs3834129 as well as their haplotype with AT risk and the identification of an optimal model which included genetic loci CASP8 _rs384129 and CASP8 _rs1045485 together with sex to capture AT risk in both SA and AUS. Collectively, these results further implicate the apoptosis signaling cascade as one of the biological pathways involved in the development of AT. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1719–1724, 2012