الفهرس 
Introduction and Aim of the workOnly 14 pages are availabe for public view
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Abstract
Osteoporosis is a systemic skeletal disease. It is the most prevalent metabolic bone disorder among developed countries. It is characterized by low bone mass, disturbed microarchitecture of bone tissue and susceptibility to nontraumatic fracture. It is estimated that it can affect 30% of women and 12% of men.
Primary osteoporosis is the most common type of osteoporosis. It is more common in women than men.
A genetic contribution to the pathogenesis of osteoporosis has recently been recognized. The VDR was the first candidate gene to be studied in relation to osteoporosis. Variants of the gene encoding VDR, recognized by ApaI (allele A/a), BsmI (allele B/b), FokI (allele F/f) and TaqI (allele T/t) restriction endonucleases, have been associated with Bone Mineral Density (BMD) in many studies as well as with bone loss in elderly subjects and gain after 1, 25-dihydroxy Vitamin D3 treatment. The FokI polymorphism is a C / T transition polymorphism (ATG to ACG) at the first of two potential translation initiation sites in exon II has been detected by using the FokI restriction endonuclease. The TaqI polymorphism is a T/C nucleotide substitution (ATT to ATC) leading to a synonymous change at codon 352 (isoleucine) in exon 9. BsmI and ApaI restriction site polymorphisms occur in the intron separating exons 8 and 9.The aim of this study was to investigate the correlation of vitamin D receptor gene polymorphisms to bone mineral density and to estimate the frequencies of those different polymorphic genotypes in an Egyptian study.
The study included 65 Egyptian females (age group 30-60 years) with primary osteoporosis and 30 age-matched normal female subjects. A detailed medical history was obtained excluding all other causes of secondary osteoporosis. All patients and controls were subjected to DEXA scan examination. Blood samples were taken for genomic DNA extraction using the standard salting-out procedure. Genotyping of the four VDR gene polymorphisms (FokI, TaqI, BsmI and ApaI) was carried out using PCR- restriction fragment length polymorphism analysis (PCR-RFLP).
Statistical analysis was performed. The complied data were computerized and analyzed by SPSS. The following tests of significance were used: analysis of variance (ANOVA) test between more than 2 means, t-test between means was used to analyze mean difference. Comparison of qualitative data was done using chi square test and cross tabs. A level of significance with p ≤ 0.05was considered significant, p ≤ 0.01was considered of high significance and p > 0.05 insignificant.
The frequencies of the different polymorphisms that the FokI frequencies were (63.1%), (27.7%), (9.2%) for FF, Ff and ff in osteoporotic patients respectively, while in the control group the frequencies were (66.7%), (30%) and (3.3%).
The frequencies of TaqI genotypes TT, Tt and tt in osteoporotic patients were 23.1%, 53.8%, 23.1% respectively, while in the control group the frequencies were 33.3%, 60% and 6.7%. The frequencies ApaI genotypes AA, Aa and aa in osteoporotic patients were (32.3%), (60.0%) and (7.7%) while in the control group the frequencies were (33.3%), (53.3%) and (13.3%) The frequencies BsmI genotypes BB, Bb and bb in osteoporotic patients were (36.9%), (38.5%), (24.6%) respectively, while in the control group the frequencies were (23.3%), (53.3%) and (23.3%).
The most significant VDR variant in FokI was the Ff genotype (p=0.007), in TaqI, was the tt genotype (p=0.002), in ApaI was the Aa genotype (p=0.002) and in BsmI was the BB genotype (p=0.002).
Combining the different genotypes showed that TtFFAa, ttFFAA, ttAABB, ttFFBB, FFAabb, ttFFAABB were the most specific haplotypes associated with osteoporosis.
In conclusion, the study proved that the four polymorphisms chosen were associated with osteoporosis and several community specific profiles were found that may be indicators for susceptibility of osteoporosis.