Molecular genetic studies of arterial aneurysms and arterial dissection diseases

Barakat, Waseem (2006) Molecular genetic studies of arterial aneurysms and arterial dissection diseases. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

I hypothesise that a major gene and/or genes are involved in the onset of aneurysms. One of the candidate genes is the elastin gene (ELN). A genealogical study may help in explaining the genetic model of some familial aneurysms. In addition, it may link apparently unrelated kindred’s together potentially to give more powerful linkage analysis of single extended kindred’s (founder effect).

Results and Conclusions: 1. No significant association was found between haplotypes in Sporadic SAH and control groups; 2. One exonic mutation was found in exon 20, six mutations were found in the intronic regions of the ELN gene; 3. Genotyping results of the exon 20 SNP using about 3000 samples of the British Women’s heart and Health Study (BWHHS) evidenced a possible association with stroke, more analysis is required using at least 10,000 sample of a case-control stoke cohort; 4. No significant association between ELN GT microsatellite in sporadic and familial SAH vs. control in the following five models: additivity model; major expansion model (anticipation); recessive model; loss of heterozygosity model and dominant model; 5. Elastin gene (the coding system) may not be associated with the intracranial aneurysm; 6. SAH may be associated with the elastin gene in different ethnicities; 7. Three novel mutations/SNPs and one known SNP were detected in the 5’ region; 8. More studies are required to investigate the possibility of 5’ mutations involvement in the onset of SAH; 9. ELN (in SAH) may be associated with the mRNA stability or the amount of mRNA of elastin or unusual alternative splicing; 10. TGFβRII may be linked with SAH in the one French family; 11. Microsatellite studies of a dinucleotide within the TGFβRII gene did not show association with sporadic SAH in any model; 12. Two penta nucleotides and two exonic SNPs were detected in the FBNI gene; a study has shown a positive association between ATTTT (which is the complementary of TAAAA in my study) and pulls pressure in over 50 years. Future analysis on a stroke cohort and functional analysis may be needed.