Stromal Derived Factor-1 Gene Polymorphism in Pediatric Immune Thrombocytopenia

Abstract

Immune thrombocytopenia (ITP) is a multifactorial disease in which both environmental and genetic factors have been implicated. The study aimed to investigate a possible association of single nucleotide polymorphisms (SNPs rs266085 and rs2839693) in the stromal derived factor-1 (SDF-1) gene and its association to ITP and effect on ITP severity and response to treatment. Genomic DNA was extracted from peripheral blood and polymorphism in SDF-1 gene rs266085 and rs2839693 was analyzed using PCR-restriction fragment length polymorphism technique in DNA extracted from 60 children with ITP together with 90 healthy controls. On analysis of SDF-1 rs266085 polymorphism, there was a high frequency of CC genotype in cases than controls and that difference was significant at codominant, overdominant, and dominant models (P<0.05). Furthermore, carriers of the CC genotype were more susceptible to severe ITP at onset, steroid dependency, and chronicity than carriers of other genotypes (P<0.05). Otherwise, no significant differences between ITP patients and controls as regard SDF-1 rs2839693 genotypes and alleles, and we did not find a relation between this polymorphism and ITP severity, steroid dependency, or duration. SDF-1 gene rs266085 SNP C allele is associated with susceptibility to develop ITP as well as increases the risk for severe ITP at onset, chronic ITP and steroid dependency.

Single Nucleotide Polymorphisms of the HIF1A Gene are Associated With Sensitivity of Glucocorticoid Treatment in Pediatric ITP Patients

“…48 So, the specific SNP may not be associated with the development of CITP in this cohort. In addition, SNPs (STAT1, 1 TNFβ, 9 IL-17F, 12,13 SDF1, 10 and FCGRIIb 14 ) associated with development of CITP are different from SNPs (SIRT1, 15 SDF1, 10,16 ABCB1, 17 TNFα, 18 and IL-23R 19 ) associated corticosteroid sensitivity except SDF1. Therefore, studies on ITP chronicity and treatment-sensitivity should be carried out separately.…”

“…Recently, many studies have identified genes associated with the risk of glucocorticoid treatment failure and development of CITP include SIRT1 (rs12778366 and rs4746720), 15 SDF1 (rs266085), 10,16 ABCB1 (C1235T, G2677T/A, and C3435T), 17 TNFα (-308AG) 18 and IL-23R (rs1884444). 19 In our previous study, we demonstrated that the percentage of Th17/Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage.…”

“…In addition, associations of ITP severity with TNFβ ,9 SDF1 ,10 and IL-10 11 have been reported. SNPs of STAT1 ,1 TNFβ ,9 IL-17F ,12,13 SDF1 ,10 and FCGRIIb 14 are associated with development of chronic ITP (CITP). These SNPs might represent a useful predictive biomarker of the disease course.…”

“…Genome-wide association studies concerned copy-number, inflammation-related and checkpoint-related susceptibility locus associated with ITP 6–8. In addition, associations of ITP severity with TNFβ ,9 SDF1 ,10 and IL-10 11 have been reported. SNPs of STAT1 ,1 TNFβ ,9 IL-17F ,12,13 SDF1 ,10 and FCGRIIb 14 are associated with development of chronic ITP (CITP).…”

“…These SNPs might represent a useful predictive biomarker of the disease course. The SIRT1 ,15 SDF1 ,10,16 ABCB1 ,17 TNFα ,18 and IL-23R 19 genes have been associated with therapy resistance especially corticosteroid sensitivity.…”