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Title: An investigation into candidate genes for abdominal aortic aneurysms
Author: Rayt, Harjeet Singh
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2013
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There is growing evidence to suggest that abdominal aortic aneurysm (AAA) is a complex disease with multiple environmental and genetic risk factors. Susceptibility genes have been investigated through multiple underpowered candidate gene studies, which has led to the association of numerous genes with conflicting evidence. This study aimed to investigate the commonly cited associations between polymorphisms of the matrix metalloproteinase-9; MMP9(-1562C > T), tissue inhibitor of metalloproteinase-1; TIMP1(+434C > T) and TIMP1(rs2070584), platelet activating factor acetylhydrolase; PLA2G7(- 994G > T), estrogen receptor beta; ESR2(+1730 A-G) and Heme oxygenase 1; HMOX1(GT)n genes and AAA in a large powered study to provide definitive evidence of any association. Materials & Methods: A case-control study was performed of 1,202 patients with AAA and 1,059 screened control subjects. DNA was extracted from whole blood and genotyping was performed using polymerase chain reaction based restriction fragment length polymorphisms (PCR-RFLP). Results Two polymorphisms (ESR2 (OR 1.42, P < 0.0001) and HMOX1 (OR 1.99, P < 0.0001)) showed a potential association with AAA. One polymorphism (TIMP1 rs2070584) could not be genotyped despite using 2 different methods. Polymorphisms of the MMP9 (OR 0.99, P=0.82), PLA2G7 (OR 0.76, P=0.29) and TIMP1 (+434C > T) (OR 0.94, P=0.46) genes did not show an association with AAA. Conclusion: We have demonstrated an association between polymorphisms of the ESR2 and HMOX1 genes and AAA, although further work is essential to confirm this association. Contrary to other published data, no such association was seen in common polymorphisms of the MMP9, TIMP1, and PLA2G7 genes and AAA.
Supervisor: Sayers, Robert ; Bown, Matthew Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available