| dc.contributor.advisor | Siggelkow, Heide Prof. Dr. | |
| dc.contributor.author | Mergler-Etmanski, Michael Helmut | |
| dc.date.accessioned | 2019-01-31T09:55:08Z | |
| dc.date.available | 2019-02-20T23:50:06Z | |
| dc.date.issued | 2019-01-31 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-002E-E57B-7 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7258 | |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Rolle von Single-Nukleotid-Polymorphismen der 11beta-Hydroxysteroid-Dehydrogenase in Bezug auf den Glucocorticoidstoffwechsel im Knochen – Einfluss auf den supprimierten Cortisolspiegel und die Knochendichte bei Osteoporosepatienten | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | Genetic polymorphisms in 11ß-hydroxysteroid dehydrogenase HSD11B1 influence dexamethasone suppressed cortisol levels as possible pathogenetic factor of bone mineral density in osteoporosis patients | de |
| dc.contributor.referee | Bickeböller, Heike Prof. Dr. | |
| dc.date.examination | 2019-02-13 | |
| dc.description.abstracteng | The enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11βHSD1) is expressed in osteoblasts and converts inactive cortisone into active cortisol. This enzymatic expression increases with age, suggesting the presence of higher cortisol levels in older persons. We hypothesised that common polymorphisms in HSD11B1 and HSD11B2 genes may cause interindividual variation in post-dexamethasone cortisol (PDC) levels and, as a result, may influence bone mineral density (BMD) and fracture risk. We performed a retrospective study of 452 ambulatory osteoporotic patients. We investigated 16 SNPs in the HSD11B1 and HSD11B2 genes for associations with PDC, BMD (primary end points), and fracture risk (secondary end point) in a subgroup of 304 patients and validated the findings in a subgroup of 148 patients. The hypothesis was formulated prior to the SNP analyses.
PDC levels were positively correlated with age and were negatively correlated with BMD at the femoral neck (R>0.274, n=287, p<0.00001). Three genetically linked SNPs in Intron 5 of HSD11B1 – rs1000283, rs932335, and rs11811440 – showed significant associations with BMD, with rs11811440 showing the highest effects. The minor A allele in rs11811440 was negatively correlated with PDC levels (R=-0.128, p=0.03, n=304) and was positively correlated with spinal BMD (R=0.17, p<0.01,
21 n=452) and with the incidence of fewer peripheral fractures in the primary osteoporosis subgroup (R=-0.138, p=0.045, n=210). SNP effects on BMD were higher in the subgroups with secondary osteoporosis and ≥ 65 years. Our data suggest a functional role of physiological cortisol metabolism for BMD in ageing and
osteoporotic patients. | de |
| dc.contributor.coReferee | Schön, Margarete Prof. Dr. | |
| dc.subject.eng | osteoporosis | de |
| dc.subject.eng | post-dexamethasone cortisol | de |
| dc.subject.eng | 11ß-hydroxysteroid dehydrogenase | de |
| dc.subject.eng | HSD11B1 | de |
| dc.subject.eng | single-nucleotide polymorphisms | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-002E-E57B-7-4 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Endokrinologie (PPN619875836) | de |
| dc.description.embargoed | 2019-02-20 | |
| dc.identifier.ppn | 1048188647 | |