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The importance of genetic factors for the development of arthropathy : A longitudinal study of children and adolescents with haemophilia A

Gomperts, Edward D; Schwarz, John; Donfield, Sharyne M.; Lail, Alice E.; Astermark, Jan LU ; Keith Hoots, W.; Winkler, Cheryl A. and Berntorp, Erik LU (2017) In Thrombosis and Haemostasis 117(2). p.277-285
Abstract

Haemophilia A is a congenital bleeding disorder characterised by recurrent haemorrhages into the major joints. Haemophilic arthropathy is a well-established outcome of recurrent joint bleeding; however, it is clear that multiple factors determine the extent and severity of its occurrence. We sought to identify genetic factors related to abnormalities in range of motion (ROM) in the knees, ankles and elbows in a cohort of children and adolescents with haemophilia A not treated primarily with regular prophylaxis. Using data from the Haemophilia Growth and Development Study, we examined associations between 13,342 genetic markers and ROM scores measured at six-month intervals for up to seven years. As a first step, ordered logistic... (More)

Haemophilia A is a congenital bleeding disorder characterised by recurrent haemorrhages into the major joints. Haemophilic arthropathy is a well-established outcome of recurrent joint bleeding; however, it is clear that multiple factors determine the extent and severity of its occurrence. We sought to identify genetic factors related to abnormalities in range of motion (ROM) in the knees, ankles and elbows in a cohort of children and adolescents with haemophilia A not treated primarily with regular prophylaxis. Using data from the Haemophilia Growth and Development Study, we examined associations between 13,342 genetic markers and ROM scores measured at six-month intervals for up to seven years. As a first step, ordered logistic regression models were fit for each joint separately. A subset of SNP markers showing significant effects (p < 0.01) on the right and left sides for at least two joints were included in a full model fit using a multivariate generalised linear mixed model assuming an ordinal response. The models contained all ROM scores obtained at all visits. Twenty-five markers analysed in the full model showed either increased or decreased risk of ROM abnormalities at the p<0.001 level. Several genes identified at either the first or second stage of the analysis have been associated with arthritis in a variety of large studies. Our results support the likelihood that risk for haemophilic arthropathy is associated with genetic factors, the identification of which holds promise for further advancing the individualisation of treatment.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Arthritis, Genetics, Haemarthrosis, Haemophilia, Joint range of motion
in
Thrombosis and Haemostasis
volume
117
issue
2
pages
9 pages
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • scopus:85011092548
  • pmid:27929201
  • wos:000393358700010
ISSN
0340-6245
DOI
10.1160/TH16-06-0440
language
English
LU publication?
yes
id
71c0b4b3-435d-40ef-843d-fe9d11167144
date added to LUP
2017-02-16 15:59:31
date last changed
2018-01-07 11:50:31
@article{71c0b4b3-435d-40ef-843d-fe9d11167144,
  abstract     = {<p>Haemophilia A is a congenital bleeding disorder characterised by recurrent haemorrhages into the major joints. Haemophilic arthropathy is a well-established outcome of recurrent joint bleeding; however, it is clear that multiple factors determine the extent and severity of its occurrence. We sought to identify genetic factors related to abnormalities in range of motion (ROM) in the knees, ankles and elbows in a cohort of children and adolescents with haemophilia A not treated primarily with regular prophylaxis. Using data from the Haemophilia Growth and Development Study, we examined associations between 13,342 genetic markers and ROM scores measured at six-month intervals for up to seven years. As a first step, ordered logistic regression models were fit for each joint separately. A subset of SNP markers showing significant effects (p &lt; 0.01) on the right and left sides for at least two joints were included in a full model fit using a multivariate generalised linear mixed model assuming an ordinal response. The models contained all ROM scores obtained at all visits. Twenty-five markers analysed in the full model showed either increased or decreased risk of ROM abnormalities at the p&lt;0.001 level. Several genes identified at either the first or second stage of the analysis have been associated with arthritis in a variety of large studies. Our results support the likelihood that risk for haemophilic arthropathy is associated with genetic factors, the identification of which holds promise for further advancing the individualisation of treatment.</p>},
  author       = {Gomperts, Edward D and Schwarz, John and Donfield, Sharyne M. and Lail, Alice E. and Astermark, Jan and Keith Hoots, W. and Winkler, Cheryl A. and Berntorp, Erik},
  issn         = {0340-6245},
  keyword      = {Arthritis,Genetics,Haemarthrosis,Haemophilia,Joint range of motion},
  language     = {eng},
  number       = {2},
  pages        = {277--285},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {The importance of genetic factors for the development of arthropathy : A longitudinal study of children and adolescents with haemophilia A},
  url          = {http://dx.doi.org/10.1160/TH16-06-0440},
  volume       = {117},
  year         = {2017},
}