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

doi:10.1016/j.gene.2015.06.010

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

University of Northampton

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

32 Downloads (Pure)

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 effects 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 (χ(2)) tests and ANOVA to detect significant associations. For our entire cohort, we found no association between the TNFRSF1A rs4149577 (p=0.561), CASP3 rs1049253 (p=0.643) and CASP8 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 language	English
Pages (from-to)	167-171
Number of pages	5
Journal	Meta Gene
Volume	571
Issue number	2
DOIs	https://doi.org/10.1016/j.gene.2015.06.010
Publication status	Published - 25 Oct 2015
Externally published	Yes

Bibliographical note

NOTICE: this is the author’s version of a work that was accepted for publication in Meta gene. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Meta gene, [571, 2, (2015)] DOI: 10.1016/j.gene.2015.06.010

© 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

Achilles Tendon
Adult
Apoptosis
Case-Control Studies
Caspase 3
Caspase 8
European Continental Ancestry Group
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Receptors, Tumor Necrosis Factor, Type I
Risk Factors
Tendinopathy
United Kingdom
Journal Article
Research Support, Non-U.S. Gov't

Access to Document

10.1016/j.gene.2015.06.010

Post-PrintAccepted author manuscript, 469 KBLicence: CC BY-NC-ND

Cite this

@article{65c9704837374a839e1e4ee16e9b1bd2,

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 effects 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 (χ(2)) tests and ANOVA to detect significant associations. For our entire cohort, we found no association between the TNFRSF1A rs4149577 (p=0.561), CASP3 rs1049253 (p=0.643) and CASP8 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 = "Achilles Tendon, Adult, Apoptosis, Case-Control Studies, Caspase 3, Caspase 8, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Tumor Necrosis Factor, Type I, Risk Factors, Tendinopathy, United Kingdom, Journal Article, Research Support, Non-U.S. Gov't",

author = "Rebecca Rickaby and {El Khoury}, Louis and Ribbans, {William J} and Raleigh, {Stuart M}",

note = "NOTICE: this is the author{\textquoteright}s version of a work that was accepted for publication in Meta gene. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Meta gene, [571, 2, (2015)] DOI: 10.1016/j.gene.2015.06.010 {\textcopyright} 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ ",

year = "2015",

month = oct,

day = "25",

doi = "10.1016/j.gene.2015.06.010",

language = "English",

volume = "571",

pages = "167--171",

journal = "Meta Gene",

issn = "2214-5400",

publisher = "Elsevier",

number = "2",

}

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

N1 - NOTICE: this is the author’s version of a work that was accepted for publication in Meta gene. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Meta gene, [571, 2, (2015)] DOI: 10.1016/j.gene.2015.06.010 © 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

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 effects 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 (χ(2)) tests and ANOVA to detect significant associations. For our entire cohort, we found no association between the TNFRSF1A rs4149577 (p=0.561), CASP3 rs1049253 (p=0.643) and CASP8 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 effects 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 (χ(2)) tests and ANOVA to detect significant associations. For our entire cohort, we found no association between the TNFRSF1A rs4149577 (p=0.561), CASP3 rs1049253 (p=0.643) and CASP8 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.

KW - Achilles Tendon

KW - Adult

KW - Apoptosis

KW - Case-Control Studies

KW - Caspase 3

KW - Caspase 8

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Receptors, Tumor Necrosis Factor, Type I

KW - Risk Factors

KW - Tendinopathy

KW - United Kingdom

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.gene.2015.06.010

DO - 10.1016/j.gene.2015.06.010

M3 - Article

C2 - 26055088

SN - 2214-5400

VL - 571

SP - 167

EP - 171

JO - Meta Gene

JF - Meta Gene

IS - 2

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this