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Polymorphisms in the IL-10 but not in the IL-1{beta} and IL-4 genes are associated with inhibitor development in patients with hemophilia A.

Astermark, Jan LU ; Oldenburg, Johannes; Pavlova, Anna; Berntorp, Erik LU and Lefvert, Ann-Kari (2006) In Blood 107(8). p.3167-3172
Abstract
The aim of the Malmö International Brother Study (MIBS) is to evaluate host genetic factors associated with the development of inhibitory antibodies in patients with hemophilia. Factor VIII gene mutations and genetic polymorphisms of the IL1beta, IL4, and 100 genes, known to influence antibody production in autoimmune diseases, were analyzed in 164 patients (124 with severe, 26 with moderate, and 14 with mild disease) in 78 unrelated families with hemophilia A. Seventy-seven (47%) patients in 54 families had a history of inhibitors (57 high responding, 20 low responding). Inversions were found in 36 families (75 patients). There was no association between the development of inhibitor and the IL1beta Taql RFLP alleles in exon 5 or the -590... (More)
The aim of the Malmö International Brother Study (MIBS) is to evaluate host genetic factors associated with the development of inhibitory antibodies in patients with hemophilia. Factor VIII gene mutations and genetic polymorphisms of the IL1beta, IL4, and 100 genes, known to influence antibody production in autoimmune diseases, were analyzed in 164 patients (124 with severe, 26 with moderate, and 14 with mild disease) in 78 unrelated families with hemophilia A. Seventy-seven (47%) patients in 54 families had a history of inhibitors (57 high responding, 20 low responding). Inversions were found in 36 families (75 patients). There was no association between the development of inhibitor and the IL1beta Taql RFLP alleles in exon 5 or the -590 C/T single nucleotide polymorphism (SNP) in the promoter region of IL4. There was, however, a strong association between an allele with 134 bp in one of the CA repeat microsatellites, IL10G, located in the promoter region of the IL10 gene, and the development of inhibitor (odds ratio [OR], 4.4; 95% confidence interval [95% CI], 2.1-9.5; P < .001). The association was consistent in the subgroup of families with severe hemophilia and inversions. IL10 is the first gene located outside the causative factor VIII gene mutation to be associated with inhibitor development. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
107
issue
8
pages
3167 - 3172
publisher
American Society of Hematology
external identifiers
  • pmid:16380445
  • wos:000236833500032
  • scopus:33645751563
ISSN
1528-0020
DOI
10.1182/blood-2005-09-3918
language
English
LU publication?
yes
id
d14d7b4d-85b8-47ee-be1e-153127745dcb (old id 148468)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16380445&dopt=Abstract
date added to LUP
2007-07-11 14:22:22
date last changed
2019-05-19 03:34:21
@article{d14d7b4d-85b8-47ee-be1e-153127745dcb,
  abstract     = {The aim of the Malmö International Brother Study (MIBS) is to evaluate host genetic factors associated with the development of inhibitory antibodies in patients with hemophilia. Factor VIII gene mutations and genetic polymorphisms of the IL1beta, IL4, and 100 genes, known to influence antibody production in autoimmune diseases, were analyzed in 164 patients (124 with severe, 26 with moderate, and 14 with mild disease) in 78 unrelated families with hemophilia A. Seventy-seven (47%) patients in 54 families had a history of inhibitors (57 high responding, 20 low responding). Inversions were found in 36 families (75 patients). There was no association between the development of inhibitor and the IL1beta Taql RFLP alleles in exon 5 or the -590 C/T single nucleotide polymorphism (SNP) in the promoter region of IL4. There was, however, a strong association between an allele with 134 bp in one of the CA repeat microsatellites, IL10G, located in the promoter region of the IL10 gene, and the development of inhibitor (odds ratio [OR], 4.4; 95% confidence interval [95% CI], 2.1-9.5; P &lt; .001). The association was consistent in the subgroup of families with severe hemophilia and inversions. IL10 is the first gene located outside the causative factor VIII gene mutation to be associated with inhibitor development.},
  author       = {Astermark, Jan and Oldenburg, Johannes and Pavlova, Anna and Berntorp, Erik and Lefvert, Ann-Kari},
  issn         = {1528-0020},
  language     = {eng},
  number       = {8},
  pages        = {3167--3172},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Polymorphisms in the IL-10 but not in the IL-1{beta} and IL-4 genes are associated with inhibitor development in patients with hemophilia A.},
  url          = {http://dx.doi.org/10.1182/blood-2005-09-3918},
  volume       = {107},
  year         = {2006},
}