Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Trummer, O.
Influence of three Vitamin D Associated Polymorphisms on Bone, Prostate Cancer and Mortality
[ Dissertation ] Medical University of Graz; 2013. pp. 128
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- Autor*innen der Med Uni Graz:
- Trummer Olivia
- Betreuer*innen:
- Lerchbaum Elisabeth
- Obermayer-Pietsch Barbara
- Renner Wilfried
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- Abstract:
- Background and aim: Vitamin D is known to play an important role in bone health. Muscoskeletal effects of inadequate vitamin D status have long been investigated including its impact on osteoporotic fractures. In the last several years vitamin D got popular for a series of benefical consequences. Many associations of low serum 25 hydroxyvitamin D (25-OH-vitamin D) status and extraskeletal effects such as cardiovascular disease, cancer and mortality have been observed. It remains unclear whether vitamin D is the cause of these clinical patterns or the consequence of an impaired health status. Based on recently reported genetic determinants of hypovitaminosis D I aimed to investigate (1st) the impact of three single nucleotide polymorphisms (SNPs) on Vitamin D and vitamin D related outcomes in the fields of bone, prostate cancer and mortality studies. Using these SNPs as a tool for Mendelian randomization, I wanted to elucidate (2nd) the question if low vitamin D levels are causal for higher mortality rates. Methods: Genotypes of SNPs in the group-specific component gene (GC, rs2282679), 7-dehydrocholesterol reductase gene (DHCR7, rs12785878) and cytochrome P450 IIR-1 gene (CYP2R1, rs10741657) were determined in different cohorts and investigated for 25-OH-vitamin D and vitamin D related outcomes. Results and conclusions: The GC polymorphism was the strongest genetic determinant of 25-OH-vitamin D status and was confirmed in all settings. CYP2R1 and the DHCR7 variants could be approved in the largest study with the highest power to detect statistical differences. Bone: None of the genotypes was linked to bone mineral density (BMD) or past fractures in a BMD screening study (n=342) and a prospective cohort study with 1093 nursing home residents. Carriers of the G-allele of the DHCR7 polymorphism showed an increased risk for prospective fractures. Prostate cancer: GC genotypes were not associated with biomarker based recurrence, development of metastases or overall survival in 702 prostate cancer patients. The investigated polymorphisms do not play a major role for the investigated bone and prostate cancer related endpoints. Mortality: GC, CYP2R1 and DHCR7 genotypes predicted 25-OH-vitamin D status reliably but not all-cause-, cardiovascular-, or non-cardiovascular mortality. This suggests that low 25-OH-vitamin D concentrations are associated with, but unlikely to be causal for higher mortality rates.