الفهرس 
IMMUNE THROMBOCYTOPENIC PURPURA (ITP)Only 14 pages are availabe for public view
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Abstract
Primary ITP is an autoimmune disorder characterized by isolated thrombocytopenia with a platelet count <100 × 109/L, in the absence of other causes or disorders that may be associated with thrombocytopenia. The pathogenesis of primary ITP remains incompletely understood, yet it appears to be highly multifactorial.
The primary role of miRNAs is being to regulate the translation of many genes, that are involved in a variety of cellular processes, including cell proliferation, differentiation, apoptosis, and immune processes. The miRISC contains proteins including AGO1- 4, GEMIN3, and GEMIN4 participates in mRNA inhibition or shearing of target mRNA.
The aim of our study to demonstrate the relation between rs636832 & rs2740348 SNPs of AGO1 gene and Gemin4 gene respectively and the risk to primary ITP as well as response to therapy in a cohort of Egyptian Population.
The present study was conducted on a total 100 patient with ITP Patients were diagnosed by presence of isolated thrombocytopenia (< 100 x 109/L) with absence of other causes of thrombocytopenia. They were selected among cases referred to the Hematology Outpatient Clinic of El-Demerdach Hospital, Faculty of Medicine, Ain Shams University during the period from September 2018 to December 2019.
One hundred age and sex matched unrelated Egyptian healthy volunteers were also included as a control group.
Patients in this study were 13 males (13%) and 87 females (87%) as in controls. The age of cases ranged from 18-67 years with a mean value + SD of 33.8 + 14.4 years. As well as the age of controls ranged from 18-67 years with a mean value + SD of 31.55 + 11.88 years.
Patients and controls were tested using real time PCR for detection of rs636832 & rs2740348 SNPs of AGO1 gene and Gemin4 gene respectively.
Regarding rs636832 A/G, our results showed frequencies of genotypes AA, AG, GG of cases were 5 (5%), 22 (22%), 73 (73%) respectively, compared to those of control 3 (3%), 20 (20%), 77 (77%) respectively, this was statistically not significant (P value= 0.704). Frequencies of A & G alleles in patients were compared to those of controls, was also statistically not significant (P value= 0.478).
AA genotype of rs636832 A/G seems to affect ITP onset as found at younger age (P-value=0.022). Also the frequency of AA at sampling in newely diagnosed and persistent ITP was found rather than in chronic ITP (P value= 0.044).
As regard frequency of (AA+AG) vs GG genotypes for non-cutaneous bleeding manifestations were found to be nearly statistically significant (P value= 0.066).
Regarding rs2740348 G/C, our results showed frequencies of rs2740348 G/C genotypes GG, GC, CC of cases were 0 (0%), 8 (8%), 92 (92%) respectively, compared to those of control 0 (0%), 7 (7%), 93 (93%) respectively, this was statistically not significant (P value= 0.788). As well as no statistical significance difference regarding allele comparison (P value = 1.00).
No statistically significance was observed between the genotype distribution with clinical presentations as well as treatment modalities and response.
However the need of splenectomy, TRO agonist as well as no response to treatment were observed in CC genotype only, but this was of no statistically significant (P value> 0.05). Larger studies may be required to demonstrate the possible actual relations.
LD analysis of the two SNPs revealed that there was linkage disequilibrium between rs636832 A/G & rs2740348 G/C more among ITP cases of Egyptian Population.
In conclusion, our data suggest that;
• rs636832 & rs2740348 are not considered to be a risk factor for ITP.
• AA genotype of rs636832 was shown to be related to occurrence of the disease at younger age as well as accompanied with more non cutaneous manifestations.
• CC genotype of rs2740348 genotype seemed to be associated with poor response to treatment and need to more lines of therapy to control the disease but larger number in the future cohort studies is required to verify these findings.
• LD was found between rs636832 & rs2740348 in our participants, mainly in ITP patients.
Despite some limitations, this study still contributes to the understanding of the role of AGO1 & GEMIN4 polymorphisms in the development of ITP and provides insight to their frequencies in Arab countries.
Recommendations
• Further studies of rs636832 & rs2740348 SNPs with larger number of participants.
• More studies of rs636832 & rs2740348 SNPs with other autoimmune disorders.
• Researching about other genetic variants of AGO1 gene and Gemin4 gene as well as of other microRNA biogenesis machinery genes and their correlations with autoimmune diseases.
• Correlation of genetic variants of microRNA machinery genes with clinical course and response to treatment of autoimmune disorders
• Analysis of linkage disequilibrium between micoRNA genes and their machinery genes in various diseases.
• Analysis of genetic variants of microRNA and its biogenesis pathway genes with other hematological disorders.
• As microRNA regulates translation of series of genes, so single gene of them in targeted therapy can control various diseases, this should be put under serious investigations.