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Title: Comprehensive investigation of targeted genetic regions for association with glomerulonephritis
Author: Vance, Dwaine Ryan
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
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Introduction: The glomerulonephritides are a group of heterogeneous disorders which can occur as primary kidney diseases or secondary to environmental factors or autoimmune 'diseases including vasculitis and systemic lupus erythematosus. Renal diseases demonstrate familial and ethnic differences suggesting underlying genetic influences. Previous studies have suggested there is a genetic susceptibility to glomerulonephritis. This study examined chromosome region 6q22-q27 and the mitochondrial genome for association with glomerulonephritis. Participants and Methods: Participants were recruited from the Medical Research Council / Kidney Research UK glomerulonephritis DNA bank and the Belfast Renal Transplant collection. A case-control approach was used to detect associated common variants (single nucleotide polymorphisms, copy number variation) located within chromosome 6q22-q27 and to investigate mitochondrial variation in end-stage renal disease patients attributed to biopsy-proven J munoglobulin-A nephropathy. Genotyping methods included TaqMan®,Sequenom MassARRAY iPLEX Gold®, Sanger sequencing and next generation sequencing technologies (iIIumina® GAllx). Results: Nominal genetic associations were identified in candidate gene case-control genetic association studies; however no common variant remained statistically significant after correction for multiple testing, except the SOD2 pathogenic variant (rs4880) which remained significant following meta-analysis. Furthermore, association was suggested for numerous mitochondrial variants. Stronger association was observed for renal transplant recipients with graft failure; however there was no increased burden of rare variants in this renal transplant group. Conclusion: Results from these comprehensive targeted investigations suggest common variants do not play a major role in genetic susceptibility to glomerulonephritis. However, rare variants with larger risk effects may be implicated in glomerulonephritis patients. Further research in larger study populations is warranted to fully unravel the genetic predisposition to glomerulonephritis
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available