الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hemoglobin is a tetramer molecule composed of 2 α like globin chain subunits and
2 β like globin chain subunits. In early life the β like globin are γ globins.
Thalassemia is an autosomal recessive genetic disorder resulting in deficient
synthesis of alpha or/and beta globin chains of hemoglobin (Hb) resulting in α and
β thalassemia disorders consequently. Owing to the high consanguineous marriages in
Egypt, the prevalence of thalassemia and its carriers is high. The disorder has a wide
spectrum of presentation starting from being asymptomatic trait or thalassemia minor to
being severe transfusion–dependent thalassemia major form. One of the key features of
β thalassemia is the high levels of HbF, which results from combination of γ globin chain
(instead of the deficient β globin chain) with the excess α globin chains.
MicroRNAs exert regulatory roles in gene expression through translational and
transcriptional control. Recent studies have highlighted the dysregulated expression of
some miRNAs in thalassemia, regulating the production of gamma globin.
MiR-210, also known as “hypoxamir”, is expressed ubiquitously and considered
a major “hypoxia-inducible” miRNA. MiRNA-210 was found to suppress the expression
of BCL11A (a major transcriptional repressor of the expression of γ-globin gene), thus
leading to increased γ globin production. In our study, we hypothesized that β thalassemia
as a hypoxic condition would result in elevation of miR-210 levels, leading to suppression
of BCL11A production and consequently increase the expression of γ globin and HbF.
Thirty patients had β thalassemia major (TM) (group A), 10 patients had β
thalassemia intermedia (TI) (group B) and 10 healthy volunteers as control subjects (group
C) were enrolled in our study. Ages among groups ranged between 2-40 years in group A,
between 4-31 years in group B, meanwhile the control group ages ranged between 1-42
years. Consanguinity was very high among disease groups, group A parents were (56.7%)
consanguineous, while group B parents were (70%) and no reported consanguinity among
Summary, Conclusion and Recommendations
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the parents of the control group. The deleterious impact of thalassemia major on health was
manifest in patients, where only one patient had a normal spleen size while the rest had
either enlarged spleen 17/30 (56.7%) or had a splenectomy 12/30 (40%). Eleven out of
thirty (36.7%) of the thalassemic patients had endocrinopathies. Cholelithiasis and
cholecystectomy was found in 8/30 (16.7 %) of our patients.
Hematological parameters; Hb levels, hematocrit and red blood cells counts were
significantly lower in group A and B than in controls (P= <0.001 for all). Meanwhile,
reticulocytic count and HbF were significantly higher in both groups than in controls
(P= 0.001, P= <0.001 respectively).
When we examined miR-210 plasma level among different groups in our study, no
statistically significant difference was found between control group and thalassemia group
of patients or its subgroups (Major and intermedia) although the median levels were higher
in TM than TI than controls (0.79, 0.58, 0.46 respectively). Hb level was observed to be
inverse to miR-210 levels, however, statistically was not significant. Reticulocytic count
elevation is a sign of enhanced erythropoiesis as found in thalassemia. The level of
reticulocytes in our study was increased positively with miR-210, however this correlation
was not significant P= 0.075. When we examined the correlation status between miR-210,
and Hb, HbF and ferritin levels, no significant correlation was found.
Nine out of thirty patients having thalassemia major were on hydroxyurea (only 2/9
(22.2%) were responders), while Six out of ten patients having thalassemia intermedia
received hydroxyurea treatment and all were responders (100%). Response to hydroxyurea
was assessed in our study by the overall decrease of at least 50% in the need of blood
transfusion or increase of Hb by at least 1 g/dL (in thalassemia intermedia), after 6 months
of treatment. In the current study miR-210 was slightly higher in responders than non-
responders to hydroxyurea, however, this difference was not statistically significant, P=
0.694.
Thalassemia severity in our study was classified into mild, moderate and severe
according to a scoring system by (Sripichai et al., 2008). We studied the association of
miR-210 levels with disease severity in each of the thalassemia groups (intermedia and
major) and with all thalassemia group altogether, no statistically significant association
was detected as well (P= 0.602, P= 0.187, P= 0.794 respectively).