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Title: Genetics of new onset diabetes after transplantation
Author: Benson, Katherine Angela
ISNI:       0000 0004 6423 3436
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2017
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New onset diabetes after transplantation (NODAT) is a common complication of organ transplantation. It is defined in this thesis as the new requirement for oral hypoglycaemic agents or insulin for the management of hyperglycaemia after renal transplantation. NODAT is a significant global health issue with a known genetic component This thesis aims to further explore the genetic architecture of this transplant complication. A comprehensive systematic literature review was used to establish current knowledge related to the genetics of NODAT. Meta-analyses were used to combine the results from this literature search and draw further conclusions on the possible contribution to NODAT of genetic variants previously reported to be associated with type 2 diabetes (T2D). Data was obtained using Ion Torrent sequencing techniques including a targeted sequencing panel and whole exome sequencing (WES). The literature review and meta-analyses provided a comprehensive overview of genetic variants reported to influence the development of NODAT. Three SNPs which are recognized as T2D risk factors were shown to be associated with NODAT by meta-analyses. A novel, targeted sequencing panel for genomic regions putatively involved in vitamin D regulation and metabolism was developed and shown to be effective for the identification of variants in two UK transplant populations. A total of 53 NODAT cases and 80 renal transplant controls were analysed using WES which identified 604,524 variants, seven of which reached P<1x10-5 significance when tested for association with NODAT in the genotypic test for trend. NODAT represents a serious complication of transplantation with profound health implications. This research investigated genetic factors influencing NODAT and included the design of a novel next generation sequencing panel. The identification of genetic variants associated with NODAT adds to our understanding of this transplant complication. These variants may be implicated in the biological mechanisms that result in sustained hyperglycaemia following organ transplantation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available