DNA Methyltransferase 3B Gene Promoter and Interleukin-1 Receptor Antagonist Polymorphisms in Childhood Immune Thrombocytopenia

Abstract

Primary immune thrombocytopenia (ITP) 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. In this study, we investigated the rs2424913 single-nucleotide polymorphism (SNP) (C46359T) in DNA methyltransferase 3B (DNMT3B) gene promoter and the VNTR polymorphism of IL-1 receptor antagonist (IL-1 Ra) intron-2 in 32 children (17 boys) with the diagnosis of ITP and 64 healthy individuals. No significant differences were found in the genotype distribution of DNMT3B polymorphism between the children with ITP and the control group, whereas the frequency of allele T appeared significantly increased in children with ITP (P = 0.03, OR = 2, 95% CI: 1.06–3.94). In case of IL-1 Ra polymorphism, children with ITP had a significantly higher frequency of genotype I/II, compared to control group (P = 0.043, OR = 2.60, 95% CI: 1.02–6.50). Moreover, genotype I/I as well as allele I was overrepresented in the control group, suggesting that allele I may have a decreased risk for development of ITP. Our findings suggest that rs2424913 DNMT3B SNP as well as IL-1 Ra VNTR polymorphism may contribute to the susceptibility to ITP.

Cytokine gene polymorphism [tumor necrosis factor-alpha (–308), IL-10 (–1082), IL-6 (–174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities

“…However, the authors did not find any significant difference between ITP and healthy control groups in terms of IL-10 (-1082,-819,-592) and IL-6 (-174) polymorphisms. Similar results regarding IL-1 Ra polymorphism were found in a study conducted by Pesmatzoglou et al [5] who investigated VNTR polymorphism of IL-1 receptor antagonist (IL-1 Ra) intron-2 in 32 children with the diagnosis of ITP and 64 healthy individuals in Greece. They reported that children with ITP had a significantly higher frequency of genotype A1A2 compared to control group and that the presence of allele A2 seems to increase 2.12 times the risk for development of ITP, thus assuming that IL-1 Ra polymorphism may be involved in the pathogenesis of ITP.…”

“…Several studies have investigated so far the association between cytokine gene polymorphisms and different immune-inflammatory diseases such as psoriasis, SLE, and rheumatoid arthritis [5,15,[41][42][43]. Furthermore, IL-17F gene is an excellent candidate for chronic inflammatory disease including ulcerative colitis, Behcet's disease, asthma, and inflammatory bowel disease [43].…”

“…Among the genetic factors, polymorphisms of inflammatory cytokine genes have been related with ITP [5].…”

Gene-gene and gene-sex epistatic interactions of <i>DNMT1</i>, <i>DNMT3A</i> and <i>DNMT3B</i> in autoimmune thyroid disease

“…Potentially functional polymorphisms were identified to meet the following criteria: 1) minor allele frequency (MAF) ≥0.05 in Han Chinese Beijing; 2) located in 5′-untranslated regions (UTR), 5′ near gene, exon, and 3′-UTR. The rs2424913 SNP with an MAF 1.2% is located -149 bp from the DNMT3B gene promoter transcription start site, and is associated with childhood immune thrombocytopenia (ITP) [15]. Another rs13428812 is an intronic SNP associated with CD [12].…”

Association of DNA methyltransferase polymorphisms with susceptibility to primary gouty arthritis

“…The rs2424913 of the DNMT3B gene ��� ��g��fi����l� ���������d w��� � ��g���v� ���k �� ��l������l cancer development in the African population (37). Although the genotype distribution of DNMT3B rs2424913 demonstrated �� ��g��fi���� d���������� b��w��� ��� ���ld��� w��� ������ thrombocytopenia (ITP) and the healthy individuals, the ���q������� �� ��� T �ll�l� w��� ��g��fi����l� ��������d �� children with ITP (38). Conversely, Piotrowski et al (39) identified that the rs1550117 of DNMT3A �x��b���d � ��g��fi���� ����������� w��� SLE �� � P�l��� ����l����� w��� compared with healthy individuals, which indicated that this SNP may protect against SLE development.…”