Variation within three apoptosis associated genes as potential risk factors for Achilles tendinopathy in a British based case-control cohort

Rebecca Rickaby, Louis El Khoury, William J Ribbans, Stuart M Raleigh

    Research output: Contribution to journalArticleResearch

    Abstract

    Achilles tendon pathology (ATP) is a degenerative condition which exhibits excessive tenocyte apoptosis. Tumour necrosis factor receptor 1 (TNFR1), caspase-3 (CASP3) and caspase-8 (CASP8) are important regulators of apoptosis. To date, the effect of variation within the genes for TNFR1 and CASP3 as risk factors for ATP have not been described. There is evidence that two single nucleotide polymorphisms (SNPs) within the CASP8 gene are associated with ATP, but only in populations from the Southern Hemisphere. The primary aim of this study was to determine whether SNPs within the TNFRSF1A and CASP3 genes were associated with ATP in British Caucasians. We additionally sought to determine whether copy number variation (CNV) within the CASP8 gene was associated with ATP. We recruited 262 (131 ATP cases and 131 asymptomatic controls) Caucasian participants for this genetic association study and used quantitative PCR with chi-squared (χ2) tests and ANOVA to detect significant associations. We found no association between the TNFRSF1A rs4149577 (p = 0.561), CASP3 rs1049253 (p = 0.643) and CASP8 copy number variants (p = 0.219) and ATP. Likewise, when we tested potential interactions between gender, genotype and the risk of ATP, we found no association with the variants investigated. In conclusion, the TNFRSF1A, CASP3 and CASP8 gene variants were not associated with ATP in British Caucasians.
    Original languageEnglish
    JournalGene
    Volume571
    Issue number2
    DOIs
    Publication statusPublished - 25 Oct 2015

    Fingerprint

    Tendinopathy
    Achilles Tendon
    Apoptosis
    Pathology
    Caspase 8
    Caspase 3
    Genes
    Tumor Necrosis Factor Receptors
    Single Nucleotide Polymorphism
    Genetic Association Studies
    Analysis of Variance
    Genotype
    Polymerase Chain Reaction

    Keywords

    • Apoptosis
    • genotype
    • achilles
    • tendinopathy

    Cite this

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    title = "Variation within three apoptosis associated genes as potential risk factors for Achilles tendinopathy in a British based case-control cohort",
    abstract = "Achilles tendon pathology (ATP) is a degenerative condition which exhibits excessive tenocyte apoptosis. Tumour necrosis factor receptor 1 (TNFR1), caspase-3 (CASP3) and caspase-8 (CASP8) are important regulators of apoptosis. To date, the effect of variation within the genes for TNFR1 and CASP3 as risk factors for ATP have not been described. There is evidence that two single nucleotide polymorphisms (SNPs) within the CASP8 gene are associated with ATP, but only in populations from the Southern Hemisphere. The primary aim of this study was to determine whether SNPs within the TNFRSF1A and CASP3 genes were associated with ATP in British Caucasians. We additionally sought to determine whether copy number variation (CNV) within the CASP8 gene was associated with ATP. We recruited 262 (131 ATP cases and 131 asymptomatic controls) Caucasian participants for this genetic association study and used quantitative PCR with chi-squared (χ2) tests and ANOVA to detect significant associations. We found no association between the TNFRSF1A rs4149577 (p = 0.561), CASP3 rs1049253 (p = 0.643) and CASP8 copy number variants (p = 0.219) and ATP. Likewise, when we tested potential interactions between gender, genotype and the risk of ATP, we found no association with the variants investigated. In conclusion, the TNFRSF1A, CASP3 and CASP8 gene variants were not associated with ATP in British Caucasians.",
    keywords = "Apoptosis, genotype, achilles, tendinopathy",
    author = "Rebecca Rickaby and {El Khoury}, Louis and Ribbans, {William J} and Raleigh, {Stuart M}",
    year = "2015",
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    Variation within three apoptosis associated genes as potential risk factors for Achilles tendinopathy in a British based case-control cohort. / Rickaby, Rebecca; El Khoury, Louis; Ribbans, William J; Raleigh, Stuart M.

    In: Gene, Vol. 571, No. 2, 25.10.2015.

    Research output: Contribution to journalArticleResearch

    TY - JOUR

    T1 - Variation within three apoptosis associated genes as potential risk factors for Achilles tendinopathy in a British based case-control cohort

    AU - Rickaby, Rebecca

    AU - El Khoury, Louis

    AU - Ribbans, William J

    AU - Raleigh, Stuart M

    PY - 2015/10/25

    Y1 - 2015/10/25

    N2 - Achilles tendon pathology (ATP) is a degenerative condition which exhibits excessive tenocyte apoptosis. Tumour necrosis factor receptor 1 (TNFR1), caspase-3 (CASP3) and caspase-8 (CASP8) are important regulators of apoptosis. To date, the effect of variation within the genes for TNFR1 and CASP3 as risk factors for ATP have not been described. There is evidence that two single nucleotide polymorphisms (SNPs) within the CASP8 gene are associated with ATP, but only in populations from the Southern Hemisphere. The primary aim of this study was to determine whether SNPs within the TNFRSF1A and CASP3 genes were associated with ATP in British Caucasians. We additionally sought to determine whether copy number variation (CNV) within the CASP8 gene was associated with ATP. We recruited 262 (131 ATP cases and 131 asymptomatic controls) Caucasian participants for this genetic association study and used quantitative PCR with chi-squared (χ2) tests and ANOVA to detect significant associations. We found no association between the TNFRSF1A rs4149577 (p = 0.561), CASP3 rs1049253 (p = 0.643) and CASP8 copy number variants (p = 0.219) and ATP. Likewise, when we tested potential interactions between gender, genotype and the risk of ATP, we found no association with the variants investigated. In conclusion, the TNFRSF1A, CASP3 and CASP8 gene variants were not associated with ATP in British Caucasians.

    AB - Achilles tendon pathology (ATP) is a degenerative condition which exhibits excessive tenocyte apoptosis. Tumour necrosis factor receptor 1 (TNFR1), caspase-3 (CASP3) and caspase-8 (CASP8) are important regulators of apoptosis. To date, the effect of variation within the genes for TNFR1 and CASP3 as risk factors for ATP have not been described. There is evidence that two single nucleotide polymorphisms (SNPs) within the CASP8 gene are associated with ATP, but only in populations from the Southern Hemisphere. The primary aim of this study was to determine whether SNPs within the TNFRSF1A and CASP3 genes were associated with ATP in British Caucasians. We additionally sought to determine whether copy number variation (CNV) within the CASP8 gene was associated with ATP. We recruited 262 (131 ATP cases and 131 asymptomatic controls) Caucasian participants for this genetic association study and used quantitative PCR with chi-squared (χ2) tests and ANOVA to detect significant associations. We found no association between the TNFRSF1A rs4149577 (p = 0.561), CASP3 rs1049253 (p = 0.643) and CASP8 copy number variants (p = 0.219) and ATP. Likewise, when we tested potential interactions between gender, genotype and the risk of ATP, we found no association with the variants investigated. In conclusion, the TNFRSF1A, CASP3 and CASP8 gene variants were not associated with ATP in British Caucasians.

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