Assessment of the association between genetic polymorphisms in transforming growth factor beta and its binding protein (LTBP) with the presence and expansion of Abdominal Aortic Aneurysm

Thompson, A. R., Cooper, J. A., Jones, G. T., Drenos, F., van Bockxmeer, F. M., Biros, E, Walker, P. J., van Rij, A. M., Golledge, J., Norman, P. E., Hafez, H. and Humphries, S. E. (2009) Assessment of the association between genetic polymorphisms in transforming growth factor beta and its binding protein (LTBP) with the presence and expansion of Abdominal Aortic Aneurysm. Atherosclerosis, 209 2: 367-373. doi:10.1016/j.atherosclerosis.2009.09.073


Author Thompson, A. R.
Cooper, J. A.
Jones, G. T.
Drenos, F.
van Bockxmeer, F. M.
Biros, E
Walker, P. J.
van Rij, A. M.
Golledge, J.
Norman, P. E.
Hafez, H.
Humphries, S. E.
Title Assessment of the association between genetic polymorphisms in transforming growth factor beta and its binding protein (LTBP) with the presence and expansion of Abdominal Aortic Aneurysm
Journal name Atherosclerosis   Check publisher's open access policy
ISSN 0021-9150
Publication date 2009-10-15
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.atherosclerosis.2009.09.073
Volume 209
Issue 2
Start page 367
End page 373
Total pages 7
Editor Steve Humphries
Place of publication London, UK
Publisher Elsevier Ireland
Collection year 2010
Language eng
Subject 920103 Cardiovascular System and Diseases
1102 Cardiovascular Medicine and Haematology
C1
Formatted abstract
Objectives Abdominal Aortic Aneurysm (AAA) has a strong genetic predisposition. Transforming growth factor beta 1 (TGF-β1) is a causal factor in ascending aortic dilatation; however, a role in AAA pathology is unclear. The aim of the study was to determine whether genes coding TGF-β and its binding protein are associated with the presence and expansion of AAA.
Methods Four geographically distinct case control studies, totaling 1890 AAA cases and 3785 controls, were genotyped and compared to the presence, size and growth rate of AAA. 26 single nucleotide polymorphisms (SNPs) in 5 genes were genotyped in the UK cohort and the result was replicated in 3 independent cohorts.
Results No associations between genotypes or haplotypes and the presence of AAA disease were confirmed. Five SNPs in Latent TGF-β Binding Protein (LTBP4) and an allelic variant of TGFB3 were associated with a significant decrease in AAA growth (p ≤ 0.02), in the UK cohort. Altered growth was demonstrated in carriers of two common haplotypes of LTBP4 (+0.38 mm/year, p = 0.003; −0.41 mm/year, p = 0.02, per haplotype copy) and a single haplotype of TGFB3 (−0.53 mm/year, p = 0.05). This association with AAA growth could not be demonstrated in two other independent cohorts. Meta-analysis of AAA size and growth rates in larger AAA (≥45 mm), in all four cohorts, demonstrated a significant association with the LTBP4 21011A > T genotype (a 2% decrease in AAA diameter, or a 0.53 mm/year reduction in AAA growth rate, per T allele [p = 0.03, p = 0.01]).
Conclusion This study suggests that the LTBP4 gene may contribute to AAA progression.
Keyword Abdominal Aortic Aneurysm
Single nucleotide polymorphism
Latent transforming growth factor beta binding protein
Aneurysm expansion
Transforming growth factor beta
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
 
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