Study of Polymorphisms in DNMT3B promoter and IL-1 Ra in Childhood Idiopathic Thrombocytopenic Purpura.

Abstract 3705

Idiopathic thrombocytopenic purpura (ITP) or primary immune thrombocytopenia is one of the most common blood diseases as well as the commonest acquired bleeding disorder in childhood. Although the etiology of ITP is unclear, in the pathogenesis of the disease both environmental and genetic factors including polymorphisms of TNF-a, IL-10 and IL-4 genes have been suggested to be involved. Aim: To investigate the association of the single-nucleotide polymorphism (SNP) in DNA methyltransferase 3B (DNMT3B C46359T) gene promoter and the polymorphism of IL-1 receptor antagonist (IL-1 Ra) intron-2 with the risk of immune thrombocytopenic purpura in childhood. Methods-patients: The genomic DNA of bone marrow mononuclear cells (MNC) of 20 children with idiopathic thrombocytopenic purpura, and peripheral blood leykocytes of 20 healthy children and 40 healthy adult volunteers (blood donors), was isolated and the region of interest was amplified by PCR. Furthermore for the DNMT3B polymorphism following digestion with Avr II the products were analyzed on agarous gel. Results: The frequencies of DΝMT3B C/C, C/T, T/T genotypes and C and T alleles in children with ITP were 50%, 35%, 15%, 67.5% και 32.5%, respectively. No significant differences were found in genotype and allele distribution between children with ITP and healthy children or adults (p=0.778 and p=1, respectively). However, there was significant difference in genotypic distribution of IL-1 Ra among children with ITP and control groups: children (p=0.001) and adults (p=0.005) as well as in allelic frequencies of IL-1 Ra between the same groups (p=0.000 and p=0.005 respectively). More specifically, children with Ι/Ι genotype or I allele seem to have decreased risk of development of ITP (OR: 0.07 [0.01–0.4]) compared both to their healthy counterparts and to healthy adults (OR: 0.17 [0.05–0.54]). Moreover the presence of the I/II genotype seems to increase 8.56 times the relative risk for disease development (OR: 8.56 [2.36–30]) while the presence of the II allele 3.8 times (OR: 3.8 [1.45–9.9]). Conclusion: The SNP (C46359T) in the promoter of DNMT3B does not seem to correlate with the diagnosis of ITP whilst the polymorphism of IL-1 receptor antagonist (IL-1 Ra) intron-2 seems to have an association with the development of the disease. This finding has to be further investigated in order its role in the pathogenesis and course of immune thrombocytopenic purpura to be confirmed.