17th Annual ECSS-Congress, Bruges 2012

Abstract details

Abstract-ID: 646
Session: [OP-PM46] Molecular Biology 2
Lecture room: est
Date & time: 08.07.2017 / -
Title of the paper: The apoptosis pathway and genetic risk factors for acute and overuse injuries
Authors: Collins, M., Seale, K., Hill, L., Burger, L., Posthumus, M., September, A.
Institution: University of Cape Town
Department: Human Biology
Country: South Africa
Abstract text Introduction: The apoptosis pathway has been identified as biologically significant in the underlying pathogenesis of several degenerative conditions, such as neurodegeneration, osteoarthritis and tendinopathies. Variants within the apoptotic regulatory gene caspase-8 (CASP8) have been associated with altered risk for chronic Achilles tendinopathy (AT). Specifically, the del-C inferred haplotype constructed from rs3834129 (ins/del) and rs1045485 (G/C) was associated with reduced AT risk. The aim was to investigate the association of these CASP8 variants, together with rs13113 (T/A), with risk of other musculoskeletal injuries, specifically rotator cuff tears (RCT), ACL ruptures and carpal tunnel syndrome (CTS). Methods:  Three independent case-control cohorts were selected (1) a white South African cohort of 101 RCT cases and 101 healthy controls, (2) a Coloured South African cohort of 102 CTS cases and 148 healthy controls and (3) a Swedish cohort of 102 ACL cases and 116 healthy controls. Participants were genotyped for the three CASP8  variants using the TaqManŽ allelic discrimination method. Potential associations were determined using the programming environment R and R packages. Results: No independent genotype, allele or inferred haplotype associations were noted for any of the CASP8 variants with risk of RCT. Similarly, no independent genotype or allele associations were noted for any of the CASP8 variants with risk of ACL or non-contact ACL ruptures. The ins-G-T inferred haplotype constructed from rs3834129, rs1045485 and rs13113 was significantly associated with increased risk of ACL (p=0.029) and non-contact ACL ruptures (p=0.026) (26.8% CON, n=30; 38.8% ACL, n=40; 39.4% NON, n=29), while the ins-G-A inferred haplotype was significantly associated with decreased risk of ACL ruptures (p=0.037; 21.7% CON, n=24; 11.8% ACL, n=12). The del-C inferred haplotype constructed from rs3834129 and rs1045485 was also significantly associated with decreased risk of non-contact ACL ruptures (p=0.039; 13.5% CON, n=15; 5.6% NON, n=4). The AA genotype of the rs13113 variant was independently associated with increased risk of CTS (p=0.030; OR=5.88; 95% CI: 1.19 to 29.0), while the ins-G-A inferred haplotype was also significantly associated with increased risk of CTS (p=0.032; 6.8% CON, n=10; 13.4% CTS, n=14) Conclusion:  The novel associations of these haplotypes with additional musculoskeletal injury phenotypes further implicates CASP8 as a candidate gene for future investigation.  The significant association of the del-C inferred haplotype with decreased non-contact ACL rupture risk, and the association of the complementary ins-G-A inferred haplotype with increased CTS risk, was in alignment with previous findings whereby the del-C haplotype was significantly associated with reduced AT risk. These results implicate the apoptosis pathway as biologically significant in the underlying pathogenesis of musculoskeletal injuries. 
Topic: Molecular Biology and Biochemistry
Keyword I: Apoptosis
Keyword II: CASP8
Keyword III: ACL