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.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/148468
- author
- Astermark, Jan LU ; Oldenburg, Johannes ; Pavlova, Anna ; Berntorp, Erik LU and Lefvert, Ann-Kari
- organization
- publishing date
- 2006
- 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
- pmid:16380445
- 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
- 2016-04-01 12:03:18
- date last changed
- 2022-04-13 05:26:56
@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 < .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}}, doi = {{10.1182/blood-2005-09-3918}}, volume = {{107}}, year = {{2006}}, }