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Immune regulatory gene polymorphisms as predisposing risk factors for the development of factor VIII inhibitors in Indian severe haemophilia A patients.
- Source :
-
Haemophilia : the official journal of the World Federation of Hemophilia [Haemophilia] 2012 Sep; Vol. 18 (5), pp. 794-7. Date of Electronic Publication: 2012 May 28. - Publication Year :
- 2012
-
Abstract
- Development of inhibitors to factor VIII, a serious complication of replacement therapy in haemophilia A patients, leads to increased bleeding, morbidity and mortality. There is no data on the risk factors for inhibitor development in Indian patients with severe haemophilia A. Our aim was to study the role of immune regulatory gene polymorphisms in the development of inhibitors. Fourteen immune regulatory gene polymorphisms (IL1β, IL4, IL10, TNFA and CTLA4) were analysed in 120 patients with severe haemophilia A, i.e. 50 inhibitor positive patients, and 70 inhibitor negative control patients, by PCR-RFLP, DNA sequencing and allele-specific PCRs. The IL10 promoter 'GCC' haplotypes overall (P: 0.002, OR: 3.452, 95% CI: 1.607-7.416), and 'GCC/ATA' (P: 0.011, OR: 3.492, 95% CI: 1.402-8.696) haplotype, associated with high and intermediate IL10 production, respectively, were significantly higher in inhibitor positive patients, whereas the 'non-GCC' haplotypes overall (P: 0.002,OR: 0.290, 95% CI 0.135-0.622) and 'ATA/ATA' haplotype (P: 0.025, OR: 0.278, 95% CI: 0.096-0.802), associated with low IL10 synthesis, were significantly higher among inhibitor negative patients. The TNFA rs1799724 C/T heterozygote prevalence was significantly higher in the inhibitor positive group (P: 0.021, OR: 3.190, 95% CI: 1.273-7.990), whereas the other polymorphisms showed no statistically significant association with the presence of inhibitors. Different immune regulatory gene polymorphisms play a significant role as possible risk factors for the development of inhibitors in severe haemophilia A patients.<br /> (© 2012 Blackwell Publishing Ltd.)
- Subjects :
- Adolescent
Adult
Blood Coagulation Factor Inhibitors blood
CTLA-4 Antigen genetics
Case-Control Studies
Child
Child, Preschool
Genetic Predisposition to Disease
Haplotypes
Hemophilia A blood
Humans
India
Interleukin-10 genetics
Interleukin-1beta genetics
Interleukin-4 genetics
Male
Middle Aged
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Risk Factors
Tumor Necrosis Factor-alpha genetics
Young Adult
Blood Coagulation Factor Inhibitors genetics
Blood Coagulation Factor Inhibitors immunology
Factor VIII antagonists & inhibitors
Factor VIII immunology
Hemophilia A genetics
Hemophilia A immunology
Polymorphism, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2516
- Volume :
- 18
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Haemophilia : the official journal of the World Federation of Hemophilia
- Publication Type :
- Academic Journal
- Accession number :
- 22630053
- Full Text :
- https://doi.org/10.1111/j.1365-2516.2012.02845.x