Ανάλυση πολυμορφισμών και προσδιορισμός γονιδίων που εμπλέκονται στην οστεοπόρωση

Doctoral Dissertation uoadl:1308640 745 Read counter

Unit:
Τομέας Γενετικής και Βιοτεχνολογίας
Library of the School of Science
Deposit date:
2012-06-27
Year:
2012
Author:
Κορομηλά Θεοδώρα
Dissertation committee:
Επ. Καθηγήτρια Παναγούλα Κόλλια, Αν. Καθηγήτρια Βασιλική Αλεπόρου-Μαρίνου, Αν. Καθηγήτρια Ζωή Νταϊλιάνα
Original Title:
Ανάλυση πολυμορφισμών και προσδιορισμός γονιδίων που εμπλέκονται στην οστεοπόρωση
Languages:
Greek
Summary:
iv

Osteoporosis is a skeletal disease with multifactorial pathogenesis,
characterized by a combination of low bone mass and increase of bone fragility.
The development of osteoporosis influenced apart from a large number of
environmental factors, by genetic factors.
In this case–control study, peripheral blood samples were collected from 550
osteoporotic and 150 control postmenopausal Greek women, as well as 82 bone
samples. The aim of the present study was to: a) investigate the possible
association of three novel candidate genes, CER1, TOB1, and DKK1, with bone
mineral density (BMD) and fragility risk, b) correlate the phenotypic data and
bone markers with the above candidate genes, c) investigate the top-associated
BMD markers with GWAS, d) study the gene expression patterns of TGFβ-BMP
pathway by microarray analysis and e) analyze the mRNA-levels alterations of
BMP2, RUNX2, RANK, RANKL, OPG genes with quantitative Real-Time PCR (Q-RT-PCR).
In conclusion, CER1 gene variations play a significant role in determining BMD
and vertebral or hip fractures combined to bone markers, in postmenopausal
osteoporotic women. GWAS analysis showed a significant association between DKK1
gene and osteoporosis, which might be helpful in clinical practice to identify
patients with increased fracture risk. On the other hand, TGFβ-BMP signaling
microarray analysis reveals different expression patterns among osteoporotic
peripheral blood, osteoporotic bone samples and control peripheral blood,
confirmed by Q-RT-PCR. A combination of bone markers with the above genes’
polymorphisms and expression patterns would be useful diagnostic marker for
personalized drug therapy and fracture risk in osteoporosis.
Keywords:
Osteoporosis, SNP, Signaling pathway, Bone markers, BMD
Index:
Yes
Number of index pages:
0
Contains images:
Yes
Number of references:
165
Number of pages:
(8), 260
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