الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 153 |  |  |
| | | from | 153 | | |
Abstract
Summary & Conclusion
B-thalassemia is an inherited disorder with an autosomal recesive mode of inheritance and constitutes one of the most serious health problems worldwide and is characterized by agenetic defect in the formation of B-globin chains leads to either marked transfusion dependent anemia in the homozygous type of beta thalassemia (thalassemia major) or in the heterozygos type of the B-thalassemia (thalassemia minor) leads to mild to moderate microcytic anemia. patients with clinical severity of the disease lie between thalassemia major and thalassemia minor are defined as thalassemia intermedia.
Osteoprosis is a debilitating bone disease which characterized by reduced bone mass, microarchitectural deterioration of bone tissue and increased risk of fragility fractures.
It is well known that increased erythropoiesis in bone marrow in B-thalassemic patients results in expansion of marrow cavity and reduced bone mass and also B-thalassemia patients exhibit an unbalance in bone mineral turnover with increased resorptive rates and suppression of osteoblast activity, resulting in diminished bone mineral density (BMD) more evident in lumbar spine.
Genetic factors play an important role in the pathogenesis of osteoporosis, involving variation in several genes such as collagen type I alpha1 (COLIA1), vitamin D receptors, estrogen receptors and interlukin6 (IL-6) that regulate bone mineral density (BMD), bone shape and structure.
One of the most important candidate genes for predisposition to osteoporosis is the COLIA1 gene. SP1 binding site polymorphism in the
Summary & Conclusion
104
transcriptional control region of the COLIA1 gene causes alleles with a G-base at sp1 binding are defined as (S) while alleles with a T-base are difined as (s). Many studies have shown that patients with (s) allele are mostly have reduced bone mineral density (BMD) and increased risk of osteoporotic fracture in B-thalassemic patients in different populations (Singh K et al 2013).
Aim of the work
The aim of this study was to determine the incidence of SP1 polymorphism in the COLIA1 gene and its correlation to development of bone disorders in patients with beta thalassemia major
Patients and Methods
This case control Study was conducted in the Outpatient Clinic of Hematology unit of Pediatric Department at Beni Suef University hospitals during the study time on 40 patients with B-thalassemia major (TM) at their regular follow up visits and 40 age- and sex matched healthy children as control group.
This study included 80 subjects; they were classified into two groups:
group 1:
This group included 40 patients with B-thalassemia major (TM) at their regular follow up visits and they are undergoing blood transfusion and iron chelation therapy (desferal) which their ages range from 6-18 years.
group 2:
Summary & Conclusion
105
This group included 40 apparently healthy subjects cross matched with age and sex.
The study was approved by the ethical committee of faculty of medicine, BeniSuef University. The patients were enrolled after obtaining an informed consent from their parents.
Inclusion Criteria:
patients with B-thalassemia major (TM) were undergoing regular blood transfusion and iron chelation therapy (desferal) which their ages range from 6-18 years and apparently healthy subjects cross matched with age and sex .
Exclusion Criteria:
1) Patients with B-thalassemia major (TM) are not undergoing regular blood transfusion.
2) Patients with B-thalassemia major (TM) are not received regular iron chelation therapy.
3) Patients that are diagnosed with other causes of chronic hemolytic
4) Patients with bone disorders not due to B-thalassemia major
Clinical assessment:
All subjects were evaluated as follows:
A) Complete history taking
B) Full clinical Examination
C) Laboratory investigations:
Complete blood count (CBC) done by system XN
Summary & Conclusion
106
Haemoglobin electrophoresis done by full automated capillary electrophoresis
Serum Calcium, Phosphorous, Alkaline phosphatase levels done by Cobas 8000
COLIA1 gene polymorphism by using polymerase chain reaction – restriction fragment length polymorphism technique (PCR-RFLP).
This study showed that:
Mean value of weight and height were lower among cases than controls.
Mean value of hemoglobin was lower among cases than controls.
Mean value of calcium was lower among cases than controls.
Mean value of phosphorus was higher among cases than controls.
High alkaline phosphatase in cases than healthy control.
Summary & Conclusion
107
Conclusion
from this study, it could be concluded that:
SS (homo) (G/G) in cases and control was 27%, 75% respectively. The Ss (hetero) (G/T) in cases and control was 57.5%, 25% respectively. The ss (homo) (T/T) in cases was 15% only. The difference was statistically significant.
The frequency of bone disorders are high among children with β- Thalassemia and SP1 mutation is one of the factors that influences bone density in these patients. The findings increase the role which genotyping at SP1 site may consider an important cause for detecting the thalassemic persons with a risk of achieve osteoporosis and bone fractures that account a possible role for improvement of osteoporosis management in those thalassemic persons.