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Polymorphisms in genes involved in autoimmune disease and the risk of FVIII inhibitor development in Italian patients with haemophilia A
- Source :
- Haemophilia : the official journal of the World Federation of Hemophilia. 16(3)
- Publication Year :
- 2009
-
Abstract
- One of the most severe and important complication in the treatment of patients with haemophilia A is the formation of neutralizing antibodies (FVIII inhibitors) that inhibit the clotting activity of substituted FVIII. Both genetic and environmental factors influence the susceptibility of patients to develop inhibitors. The objective of this study was to evaluate whether polymorphisms in different genes involved in the regulation of the immune system may confer susceptibility to inhibitor development in patients with HA. We analysed the distribution of polymorphisms in the CTLA4, PTPN22, IL10, TNFalpha, FOXP3 and IRF5 genes that have been reported to be associated with a number of autoimmune disease. In addition, we evaluated the distribution of IL10 haplotypes in haemophilic patients and healthy controls to assess whether specific polymorphisms in IL10 gene were associated to the risk of inhibitor development. We focused on a cohort of Italian unrelated haemophilic patients with and without a history of inhibitors. Genotyping was carried out with standard methods including RFLP, real time PCR and direct DNA sequencing. Our data show that, considering single nucleotide variations, genotype frequencies in patients with inhibitors were not significantly different from those observed in patients without inhibitors, suggesting a lack of association between these polymorphisms and the development of inhibitors. Moreover, no relationship was found between specific combinations of IL10 alleles and the antibody production. Previous contradictory association studies may depend on the different genetic background of the population examined. Further studies may contribute to a clearer understanding of this process.
- Subjects :
- Haemophilia
Hemophilia A
Antibodies
Autoimmune Diseases
Genetic
Gene Frequency
Antigens, CD
Risk Factors
Autoimmune disease
Humans
CTLA-4 Antigen
Antigens
Polymorphism
Factor VIII
Polymorphism, Genetic
Blood Coagulation Factor Inhibitors
Inhibitors
Tumor Necrosis Factor-alpha
Forkhead Transcription Factors
Protein Tyrosine Phosphatase, Non-Receptor Type 22
Exons
Non-Receptor Type 22
CD
Interleukin-10
Italy
Interferon Regulatory Factors
Protein Tyrosine Phosphatase
Polymorphisms
Subjects
Details
- ISSN :
- 13652516
- Volume :
- 16
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Haemophilia : the official journal of the World Federation of Hemophilia
- Accession number :
- edsair.pmid.dedup....af607e90fa8f742413689ed10c67a0b9