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Identifier

000364598

Title

Αναζήτηση πολυμορφικών παραλλαγών στα γονίδια των προφλεγμονωδών κυτταροκινών TNF-α, TGF-β1 και FAS-L και διερεύνηση του πιθανού ρόλου αυτών στην παθογένεια της χρόνιας ιδιοπαθούς ουδετεροπενίας

Alternative Title

The SOP C/T polymorphism of transforming growth-factor-B is a associated with increasing risk for development of chronic idiopathic neutropenia

Author

Ηλιόπουλος, Δημήτριος

Thesis advisor

Παπαδάκη, Ελένη

Reviewer

Σταθόπουλος, Ευστάθιος
Τσατσάνης, Χρήστος
Γουλιέλμος, Γεώργιος
Ηλιόπουλος, Αριστείδης

Abstract

Objective: Impaired granulopoiesis in chronic idiopathic neutropenia (CIN) has been associated with an inflammatory bone marrow (BM) microenvironment consisting of pro-inflammatory and pro-apoptotic mediators such as tumour necrosis factor (TNF)-α, transforming growth factor(TGF)-β1 and Fas-Ligand (Fas-L). In this study we evaluated the frequency of TNF-α, TGF-β1 and Fas-L gene polymorphisms in CIN patients and explored their role in excessive cytokine production and their association with CIN development. Methods: The TNF-α -308G/A, TGF-β1 -509C/T, +869T/C, +915G/C and Fas-L -844T/C polymorphisms were studied in 57 CIN patients and 100 healthy controls from Crete, a well-defined area with genetically homogeneous population, using a polymerase chain reaction-based restriction fragment length polymorphism assay. Results: The mutant genotype C/T or T/T of TGF-β1 -509C/T polymorphism was more common in CIN patients than in controls (p=0.033). Compared to wild type genotype, the TT genotype was associated with increased risk for CIN development (OR: 5.7; 95% Confidence Intervals: 1.18-27.26; p = 0.033). Compared to controls, patients with CT and TT genotypes displayed increased TGF-β1 levels in serum (p΄&λτ0.0001 and p=0.0002, respectively) and BM (p΄&λλλλλλλτ0.0001 and p=0.0002, respectively). No significant difference was found between patients and controls in the frequency of TNF-α -308G/A, TGF-β1 +869T/C and +915G/C, and Fas-L -844T/C polymorphisms. Conclusions: The TGF-β1-509C/T polymorphism is associated with increased risk for CIN and contributes to the pathophysiology of the disorder by inducing TGF-β1 overproduction. This is the first study providing evidence that genetic factors may predispose to CIN and may have a role in the pathophysiology of the disorder.

Language

Greek

Subject

Chronic idiopathic neutropenia

Hemic lymphatic systems

Transforming growth factor-B

Αίμα λεμφικό σύστημα

Γενετικοί πολυμορφισμοί

Μετατρεπτικός αυξητικός παράγοντας-β1

Χρόνια ιδιοπαθής ουδετεροπενία

Issue date

2009-12-14