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Title: Influence of genetics and diet on the regulation of vitamin D metabolism in the elderly and its contribution to age-related macular degeneration
Author: Dollin, Kiera
ISNI:       0000 0004 2741 8175
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2012
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Age-related macular degeneration (AMD) is the leading cause of severe visual impairment and blindness in the developed world. The exact pathogenesis of AMD is unknown, however, in common with cardiovascular disease, AMD may be underpinned by chronic inflammatory processes which lead to prolonged activation of both resident and recruited macrophage-like microglial (MG) cells. Vitamin D is a prohormone which can be produced in the skin following exposure to UVB radiation. It can also be obtained from dietary sources such as oily fish and from supplements. The main circulating metabolite, 25-hydroxyvitamin D (250HD) is used to assess vitamin D status, whilst the biologically active metabolite, 1,25-dihydroxyvitamin D (1,25(OHhD) is responsible for exerting the physiological effects of vitamin D in target tissues. The main physiological role of vitamin D is in maintaining skeletal health, however, it has been suggested that vitamin D deficiency may be associated with several other health outcomes including CVD and AMD. The current study established a gold standard UPLC/MS/MS assay and used this to determine the 250HD levels of an elderly European population originally recruited to investigate the prevalence and risk factors for AMD (EUREYE). Analysis determined that no association was present between 250HD levels and late AMD in this cohort. Additionally, DNA from EUREYE subjects was used for genotyping analysis of 93 SNPs and 112 haplotypes located across 7 genes believed to be involved in the vitamin D metabolic pathway. When vitamin D status confounders were adjusted for in a linear regression model, the homozygous minor allele genotype for rs1491718 and rs16847050 in the GC gene, together with seven haplotypes in the GC gene, one in the RXRA gene and one in the CYP2R1 gene, were found to be significantly associated with 250HD levels. Further, 1,25(OH)2D3 was found to exert no significant effect on lipopolysaccharide-induced cycloxygenase-2 expression or inducible nitric oxide synthase expression or activity in the BV2 microglial cell line.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available