title: The apoptosis pathway and the genetic predisposition to Achilles tendinopathy.
abstract: 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.
authors.affiliation: MRC/UCT Research Unit for Exercise Science and Sports Medicine, Faculty of Health Sciences, Department of Human Biology, University of Cape Town, Newlands, South Africa.
authors.forename: Erica-Mari
authors.initials: EM
authors.lastname: Nell
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.forename: Jill
authors.initials: J
authors.lastname: Cook
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Handley
authors.forename: Malcolm
authors.initials: M
authors.lastname: Collins
authors.forename: Alison V
authors.initials: AV
authors.lastname: September
mesh_terms: D000125:Achilles Tendon; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D018570:Risk Assessment; D052256:Tendinopathy / Q000235:genetics*
chemical_list: C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C505530:CASP8 protein, human; D053181:Caspase 8