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VARIATIONS IN CYTOKINE GENE POLYMORPHISM AMONG EGYPTIAN CHILDREN WITH PRIMARY IMMUNE THROMBOCYTOPENIA
Author(s): ,
Galila Mokhtar
Affiliations:
Hematology and Oncology Unit, Department of Pediatrics,Ain shams University,Cairo,Egypt
,
Nagham El-beblawy
Affiliations:
Hematology and Oncology Unit, Department of Pediatrics,Ain shams University,Cairo,Egypt
,
Amira Adly
Affiliations:
Hematology and Oncology Unit, Department of Pediatrics,Ain shams University,Cairo,Egypt
,
Nancy Elbarbary
Affiliations:
Hematology and Oncology Unit, Department of Pediatrics,Ain shams University,Cairo,Egypt
,
Tarek Kamal
Affiliations:
Human Genetics Unit, Department of Pediatrics,Ain shams University,Cairo,Egypt
Esraa Hasan
Affiliations:
Hematology and Oncology Unit, Department of Pediatrics,Ain shams University,Cairo,Egypt
(Abstract release date: 05/19/16) EHA Library. Elbarbary N. 06/09/16; 132976; E1427 Disclosure(s): I have nothing to disclose
Assoc. Prof. Nancy Elbarbary
Assoc. Prof. Nancy Elbarbary
Contributions
Abstract
Abstract: E1427

Type: Eposter Presentation

Background
Childhood immune thrombocytopenia (ITP) is a common pediatric hematologic disorder with an association between the cytokine gene polymorphisms affecting the cytokine production and autoimmune diseases at the stage of formation of disease and in the course of disease and their responses to treatment.

Aims
To evaluate the possible role of  cytokine genes  as well as of  their  polymorphisms in Childhood ITP, we analyzed the allelic and genotypic frequencies of different cytokine gene polymorphisms known to be related to autoimmunity and inflammation (IL-6−174,  IL-10−1082,  IL-17F, TNF- α−308, 1RaVNTR ) in Egyptian patients with ITP and healthy control subjects. In addition we assessed the potential role of these polymorphisms in relation to phases of ITP, disease progression and response to different treatment modalities.

Methods
A total of 50 (22 males, 28 females) pediatric patients with primary ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls age and sex matched were investigated via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for cytokine gene polymorphism. Information on demographic characteristics, duration of disease, bleeding symptoms, life threatening bleeding, severity of bleeding, disease phases, type and response to different types of treatment were assessed.  

Results
Compared to controls, all patients showed a higher frequency of IL-6−174 CC ( P= 0.0001, OR = 7.048, 95% CI = 2.18-22.7), higher GA genotype of TNF-α(−308) (P= 0.001, OR = 6.469, 95% CI = 2.0-20.9), higher CC genotype of  IL-17F (P= 0.0001,OR = 55.545, 95% CI = 14.4-213.2), higher GG of  IL-10−1082 (P= 0.029, OR = 3.6, 95% CI = 1.08-12.18 ) and A1A2 genotype of  IL- 1RaVNTR (P = 0.039, OR = 2.374, 95% CI = 1.03-5.4 ). The frequency of  IL-6 (-174) C allele ( 66 % vs. 49%, P=0.015), A allele of  TNF-α−308 ( 24% vs. 6%, P=0.001), A2 allele of  IL-1RaVNTR ( 30% vs. 14%, P=0.007), IL-17F  C allele  (89% vs.53%, P=0.0001) were significantly higher in all  patients with ITP  compared to controls. However, there was no significant difference revealed in allele distribution of IL-10(-1082) (p=0.67).  IL-10 GA and IL-1Ra A1A1genotypes were higher among chronic patients (P=0.042, P=0.001 respectively) compared to newly diagnosed. There were no significant differences between different cytokine  genotypes and the various  clinical features  including  gender, age,disease duration, bleeding score, wet purpura,  life threatening bleeding among newly diagnosed ITP patients (P>0.05).On the other hand, among chronic patients with ITP, 30 % presented with mucosal bleeding (wet purpura) with highest prevalence among CC genotype (50%) followed by GC genotype (15.4%)and lastly GG genotype (0%) of IL-6 (P=0.048). Of note, the age of diagnosis of chronic patients was significantly higher than the newly diagnosed patients with ITP (2.84 versus 5.75 years(P=0.011). Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10(-1082) in all patients with ITP with P value of (P=0.001 and P=0.002 respectively).

Conclusion
This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased  risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP. However, the role of other genetic and environmental factors cannot be entirely ruled out. 

Session topic: E-poster

Keyword(s): Gene polymorphism, Idiopathic thombocytopenic purpura (ITP), Pediatric, Treatment
Abstract: E1427

Type: Eposter Presentation

Background
Childhood immune thrombocytopenia (ITP) is a common pediatric hematologic disorder with an association between the cytokine gene polymorphisms affecting the cytokine production and autoimmune diseases at the stage of formation of disease and in the course of disease and their responses to treatment.

Aims
To evaluate the possible role of  cytokine genes  as well as of  their  polymorphisms in Childhood ITP, we analyzed the allelic and genotypic frequencies of different cytokine gene polymorphisms known to be related to autoimmunity and inflammation (IL-6−174,  IL-10−1082,  IL-17F, TNF- α−308, 1RaVNTR ) in Egyptian patients with ITP and healthy control subjects. In addition we assessed the potential role of these polymorphisms in relation to phases of ITP, disease progression and response to different treatment modalities.

Methods
A total of 50 (22 males, 28 females) pediatric patients with primary ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls age and sex matched were investigated via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for cytokine gene polymorphism. Information on demographic characteristics, duration of disease, bleeding symptoms, life threatening bleeding, severity of bleeding, disease phases, type and response to different types of treatment were assessed.  

Results
Compared to controls, all patients showed a higher frequency of IL-6−174 CC ( P= 0.0001, OR = 7.048, 95% CI = 2.18-22.7), higher GA genotype of TNF-α(−308) (P= 0.001, OR = 6.469, 95% CI = 2.0-20.9), higher CC genotype of  IL-17F (P= 0.0001,OR = 55.545, 95% CI = 14.4-213.2), higher GG of  IL-10−1082 (P= 0.029, OR = 3.6, 95% CI = 1.08-12.18 ) and A1A2 genotype of  IL- 1RaVNTR (P = 0.039, OR = 2.374, 95% CI = 1.03-5.4 ). The frequency of  IL-6 (-174) C allele ( 66 % vs. 49%, P=0.015), A allele of  TNF-α−308 ( 24% vs. 6%, P=0.001), A2 allele of  IL-1RaVNTR ( 30% vs. 14%, P=0.007), IL-17F  C allele  (89% vs.53%, P=0.0001) were significantly higher in all  patients with ITP  compared to controls. However, there was no significant difference revealed in allele distribution of IL-10(-1082) (p=0.67).  IL-10 GA and IL-1Ra A1A1genotypes were higher among chronic patients (P=0.042, P=0.001 respectively) compared to newly diagnosed. There were no significant differences between different cytokine  genotypes and the various  clinical features  including  gender, age,disease duration, bleeding score, wet purpura,  life threatening bleeding among newly diagnosed ITP patients (P>0.05).On the other hand, among chronic patients with ITP, 30 % presented with mucosal bleeding (wet purpura) with highest prevalence among CC genotype (50%) followed by GC genotype (15.4%)and lastly GG genotype (0%) of IL-6 (P=0.048). Of note, the age of diagnosis of chronic patients was significantly higher than the newly diagnosed patients with ITP (2.84 versus 5.75 years(P=0.011). Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10(-1082) in all patients with ITP with P value of (P=0.001 and P=0.002 respectively).

Conclusion
This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased  risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP. However, the role of other genetic and environmental factors cannot be entirely ruled out. 

Session topic: E-poster

Keyword(s): Gene polymorphism, Idiopathic thombocytopenic purpura (ITP), Pediatric, Treatment

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