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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
Author(s) -
Pinto P.,
Ghosh K.,
Shetty S.
Publication year - 2012
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2012.02845.x
Subject(s) - haemophilia , haemophilia a , medicine , haplotype , immune system , allele , gastroenterology , genotype , immunology , haemophilia b , gene , genetics , biology , pediatrics
Summary 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 ( IL 1β, IL 4, IL 10, TNFA and CTLA 4 ) 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 PCR s. The IL 10 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 IL 10 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 IL 10 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.