A gene-centric study of common carotid artery remodelling

Harrison S.C., Zabaneh D., Asselbergs F.W., Drenos F., Jones G.T., Shah S., Gertow K., Sennblad B., Strawbridge R.J., Gigante B., Holewijn S., De Graaf J., Vermeulen S., Folkersen L., van Rij A.M., Baldassarre D., Veglia F., Talmud P.J., Deanfield J.E., Agu O., Kivimaki M., Kumari M., Bown M.J., Nyyssonen K., Rauramaa R., Smit A.J., Franco-Cereceda A., Giral P., Mannarino E., Silveira A., Syvanen A.-C., de Borst G.J., van der Graaf Y., de Faire U., Baas A.F., Blankensteijn J.D., Wareham N.J., Fowkes G., Tzoulaki I., Price J.F., Tremoli E., Hingorani A.D., Eriksson P., Hamsten A. and Humphries S.E. (2013) A gene-centric study of common carotid artery remodelling. Atherosclerosis, 226 2: 440-446. doi:10.1016/j.atherosclerosis.2012.11.002


Author Harrison S.C.
Zabaneh D.
Asselbergs F.W.
Drenos F.
Jones G.T.
Shah S.
Gertow K.
Sennblad B.
Strawbridge R.J.
Gigante B.
Holewijn S.
De Graaf J.
Vermeulen S.
Folkersen L.
van Rij A.M.
Baldassarre D.
Veglia F.
Talmud P.J.
Deanfield J.E.
Agu O.
Kivimaki M.
Kumari M.
Bown M.J.
Nyyssonen K.
Rauramaa R.
Smit A.J.
Franco-Cereceda A.
Giral P.
Mannarino E.
Silveira A.
Syvanen A.-C.
de Borst G.J.
van der Graaf Y.
de Faire U.
Baas A.F.
Blankensteijn J.D.
Wareham N.J.
Fowkes G.
Tzoulaki I.
Price J.F.
Tremoli E.
Hingorani A.D.
Eriksson P.
Hamsten A.
Humphries S.E.
Title A gene-centric study of common carotid artery remodelling
Journal name Atherosclerosis   Check publisher's open access policy
ISSN 0021-9150
1879-1484
Publication date 2013-02
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.atherosclerosis.2012.11.002
Volume 226
Issue 2
Start page 440
End page 446
Total pages 7
Place of publication Clare, Ireland
Publisher Elsevier Ireland
Collection year 2014
Language eng
Subject 2705 Cardiology and Cardiovascular Medicine
Formatted abstract
Background: Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized.
Methods: Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IMPROVE study (n = 3427) using the Illumina 200k Metabochip was performed. Single nucleotide polymorphisms (SNPs) that met array-wide significance were taken forward for analysis in three further studies (n = 5704), and tested for association with Abdominal Aortic Aneurysm (AAA).
Results: rs3768445 on Chromosome 1q24.3, in a cluster of protein coding genes (DNM3, PIGC, C1orf105) was associated with larger ICCAD in the IMPROVE study. For each copy of the rare allele carried, ICCAD was on average 0.13 mm greater (95% CI 0.08-0.18 mm, P = 8.2 × 10-8). A proxy SNP (rs4916251, R2 = 0.99) did not, however, show association with ICCAD in three follow-up studies (P for replication = 0.29). There was evidence of interaction between carotid intima-media thickness (CIMT) and rs4916251 on ICCAD in two of the cohorts studies suggesting that it plays a role in the remodelling response to atherosclerosis. In meta-analysis of 5 case-control studies pooling data from 5007 cases and 43,630 controls, rs4916251 was associated with presence of AAA 1.10, 95% CI 1.03-1.17, p = 2.8 × 10-3, I2 = 18.8, Q = 0.30). A proxy SNP, rs4916251 was also associated with increased expression of PIGC in aortic tissue, suggesting that this may the mechanism by which this locus affects vascular remodelling.
Conclusions: Common variation at 1q24.3 is associated with expansive vascular remodelling and risk of AAA. These findings support a hypothesis that pathways involved in systemic vascular remodelling play a role in AAA development.
Keyword Abdominal aortic aneurysm
Carotid artery
Genome-wide association studies
Vascular remodelling
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
 
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