الفهرس 
ThalassemiaOnly 14 pages are availabe for public view
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Abstract
β-thalassemia is a monogenic disorder usually caused by
reduced or absent synthesis of the β-globin chain, one of the main
components of adult hemoglobin. β-thalassemia is the most common
chronic hemolytic anemia in Egypt, with a carrier rate of
approximately 10%. The worldwide incidence rate is valued at one per
100,000.
Blood transfusion is a traditional treatment for β-thalassemia
that improves the patient’s anemia and lifespan, but it may lead to iron
overload in parenchymal tissue organs and endocrine glands causing
their dysfunctions as the iron regulatory system can’t excrete excess
iron from the bloodstream.
The FOXO3 transcription factors represent targets of the
phosphatidylinositol 3-kinase/protein kinase B survival pathway
controlling important biological processes, such as cell cycle
progression, apoptosis, vascular remodeling, stress responses, and
metabolism.
This study aimed to assess the role of FOXO3 gene
polymorphism rs3800231 in β-TM and its complications in children.
The study included 150 subjects, divided into 3 groups: 50 β-TM
patients without complications, 50 β-TM patients with complications
divided into cardiac complications and osteoporosis, and 50 age and
gender-matched healthy children as controls.
All patients of this study were subjected to full history taking,
clinical examination, routine investigations (complete blood count, Hb
electrophoresis, serum ferritin, ECHO cardiography, bone density by
Summary
86
DEXA scan), and specific laboratory testing (detection of FOXO3
gene polymorphism by Real-time PCR).
Our results showed that:
There was no significant difference in gender between patients
and controls. However, the β-TM group with complications was
significantly older than other groups.
Weight, height, and BMI were significantly lower in β-TM
patients than in controls. However, there was no considerable
difference between β-TM patients with complications and β-TM
patients without complications.
β-TM patients with complications had a significantly higher rate
of regular blood transfusion and higher incidence of
splenectomy than β-TM patients without complications. The
frequency of blood transfusion was significantly higher in β-TM
patients with cardiac complications than in patients with
osteoporosis.
The Hb, MCV, and MCH were significantly lower in both β-TM
patient groups than in controls. However, WBC count and PLT
count were higher in the β-TM patient groups than in controls,
with no considerable difference between β-TM patients with
complications and β-TM patients without complications.
Serum ferritin was higher in the β-TM patient groups than in
controls. Also, it was higher in the β-TM patients with
complications than β-TM patients without complications.
However, there was no considerable difference between β-TM
patients with cardiac complications and β-TM patients with
osteoporosis.
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Hb F% was significantly higher in β-TM patients with
complications than in β-TM patients without complications.
However, Hb A2% was significantly higher in β-TM patients
without complications than in β-TM patients with
complications.
In the current study, a significant difference was observed in
the genotype frequency of the FOXO3 gene rs3800231 A/G
SNP among the studied groups. The GG genotype was more
frequent among the β-TM patients without complications and β-
TM patients with complications than controls, with significant
risk for β-TM where the OR was 5.115 (95% CI: 1.62–16.14)
and risk for β-TM complications with OR of 8.48 (95% CI:
2.60-27.66). However, there was no significant difference
between β-TM patients with complications and β-TM patients
without complications.
Regarding genotype and allele distribution. AA genotype was
more frequent among controls than patient groups. As regards
allele distribution, the G allele was more frequent among the β-
TM patients without complications and β-TM patients with
complications than controls (p=0.003, <0.001 respectively), and
carried a significant risk for thalassemia complications with an
odds ratio of 3.622 (CI%: 1.20–6.58), meanwhile the A allele
was more frequent in controls with no significant difference
between the patients’ groups.
The GG genotype was significantly more frequent in β-TM
patients with cardiac complications than in β-TM patients
without complications (p=0.044).
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88
Multivariate logistic regression analysis demonstrated that the
frequency of regular blood transfusion, serum ferritin, platelets,
Hb F%, and Hb A2% were considered risk factors for β-TM
complications.
There was a significant correlation between rs3800231
polymorphism and BMI in the non-complicated β-TM group.