الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 148 |  |  |
| | | from | 148 | | |
Abstract
Thalassemia is a heterogeneous group of congenital hemoglobinopathies caused by mutations in the globin gene complex that result in an unbalanced globin synthesis.
Beta-thalassemia is the most common genetic disorder in Egypt.
The genetic disorder includes a wide variety of clinical phenotypes, ranging in severity from clinically silent heterozygous β-thalassemia to severe transfusion-dependent β-thalassemia major (β-TM).
It may be associated with changes in the bone microarchitecture leads to low bone mineral density and high prevalence of fracture.
VDR is a nuclear transcription factor, that mediates the action of 1,25(OH)2D3, thus influencing calcium absorption, bone remodeling and mineralization rate.
Vitamin D receptor gene is located on chromosome 12q13.11 and consists of 14 exons. It has an extensive promoter region capable of generating multiple tissue-specific transcripts.
Its gene variation is highly associated with dysfunctions of vitamin D. The SNP in the VDR gene can cause alteration in the structure of the VDR protein . Moreover, some variation is strongly associated with different abilities of the VDR protein to bind transcription factor II B (TFIIB), leading to divergent gene transcription coupled with VDR.
FokI (rs2228570), is localized within the 5` end of the gene. It consists of a T > C variation at translation initiation codon (ATG) in exon 2 .
The Fok-1 VDR polymorphism described by diallelic (ATG/ACG) variant in exon 2 of the gene. This variation is located on the translation initiation leads to a three amino acid difference in VDR length between two alleles that may alters the function of the VDR protein.
The minor T allele leads to the production of the long 427 amino-acid VDR proteins with lower activity than the short 424 amino acids encoded by the major C allele. As the shorter polypeptide is of higher efficiency to couple with the transcription factor II B (TFIIB) and leads to a higher transcriptional rate of vitamin dependent genes.
The aim of this study is to evaluate VDR variation and its relation with bone mineral density (BMD) values in Beta-thalassemia.
The current study was carried out on 76 children with B-thalassemia (40 boys and 36 girls) who were selected from the attendants of the Pediatric Hematology Clinic, Menoufia University Hospital, Egypt (They were on regular packed red cell transfusion) and 51 (29 boys and 22 girls), age and sex matched healthy children were involved as a control group .
All children subjected to full history taking, clinical examination. Liver and kidney functions, serum calcium, phosphorous, alkaline phosphatase and vitamin D levels measurement. BMD was determined. VDR rs2228570 SNP was assayed by real time PCR.
Subjects were divided into:-
group I :It included 76 patients with β-thalassemia.(40 boys and 36 girls) who were with a mean age of 7.55± 4.24 years.
Children with abnormal thyroid functions, abnormal renal functions, diabetes mellitus and serological evidence of hepatitis B or C were excluded from the study.
group II :Fifty one (29 boys and 22 girls), age and sex matched healthy children were involved as a control group with a mean age of 8.31 ± 4.19 year .with no history of Any individual with pallor, abnormal CBC findings, history of blood transfusion or family history of thalassemia or other hemoglobinopathies.
The current study showed:
There was a significant increase in phosphorus, alkaline phosphatase, frequency of the TT genotype and T allele of rs2228570 SNP of VDR and decrease in calcium, vitamin D levels and BMD in patients group. There was a significant increase of vitamin D levels and decrease in patients with TT genotype than both TC and CC.Also,There were significant increase in number and % of osteopenia and osteoporosis in patients group with TT genotype than both TC and CC (p<0.001).
Conclusion:
TT genotype and T allele affect vitamin D level, function and associated with decrease BMD and high frequency of osteopenia and osteoporosis in children with Beta thalassemia.