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Title: Genetic analysis of plasma von Willebrand factor antigen levels as a risk factor for arterial and venous thrombosis
Author: Bayoumy, Nervana M. K.
ISNI:       0000 0001 3452 2104
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2006
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We carried out the first genome-wide linkage analysis in British families for VWF levels. ABO and VWF loci were specifically examined. The results showed that VWF levels are highly heritable 42% ( P>0.000001) with age and C-reactive protein (CRP) the main covariates. The ABO locus was strongly associated with VWF levels ( P=2x10-18), but linkage was modest (LOD = 1.6). VWF gene marker showed no significant association or linkage with phenotype. Genome-wide linkage analysis, conditioned on age and ABO genotypes, revealed regions with potential linkage. Highlighted regions were on chromosomes 2 and 3 (LOD = 1.78 & 1.08 respectively) and two areas on chromosome 12 (LOD = 1.5 & 1.3). Inflammatory biomarkers concentrations were also investigated. Heritabilities of CRP and tumour necrosis factor-alpha (TNF-alpha) were significantly high 38% and 47% respectively, while interleukin-6 was not heritable. VWF levels showed significant genetic correlation with CRP. As ABO group has a major role in determining VWF levels, if the VWF stroke association is causal, blood groups should be associated with stroke (Mendelian Randomisation). ABO genotype frequencies in stroke patients were investigated by a case-control study (503 objectively diagnosed cases and 327 controls). Non-O groups were not significantly over-represented in stroke cases (OR 1.1, CI95 0.83--1.47). Monte Carlo method, taking into account ABO effect on VWF levels, showed no association between ABO genotypes and stroke risk. This was reinforced by the findings of the systematic review we conducted on ABO groups and stroke. In contrast to results obtained from venous TE systematic review, where almost a two fold increased risk was found with non-O groups vs. O group.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available