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A gene-centric study of common carotid artery remodelling.


ABSTRACT: Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized.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).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, R(2) = 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), I(2) = 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.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.

SUBMITTER: Harrison SC 

PROVIDER: S-EPMC3573227 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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A gene-centric study of common carotid artery remodelling.

Harrison Seamus C SC   Zabaneh Delilah D   Asselbergs Folkert W FW   Drenos Fotios F   Jones Gregory T GT   Shah Sonia S   Gertow Karl K   Sennblad Bengt B   Strawbridge Rona J RJ   Gigante Bruna B   Holewijn Suzanne S   De Graaf Jacqueline J   Vermeulen Sita S   Folkersen Lasse L   van Rij Andre M AM   Baldassarre Damiano D   Veglia Fabrizio F   Talmud Philippa J PJ   Deanfield John E JE   Agu Obi O   Kivimaki Mika M   Kumari Meena M   Bown Matthew J MJ   Nyyssönen Kristiina K   Rauramaa Rainer R   Smit Andries J AJ   Franco-Cereceda Anders A   Giral Philippe P   Mannarino Elmo E   Silveira Angela A   Syvänen Ann-Christine AC   de Borst Gert J GJ   van der Graaf Yolanda Y   de Faire Ulf U   Baas Annette F AF   Blankensteijn Jan D JD   Wareham Nicholas J NJ   Fowkes Gerry G   Tzoulaki Ionna I   Price Jacqueline F JF   Tremoli Elena E   Hingorani Aroon D AD   Eriksson Per P   Hamsten Anders A   Humphries Steve E SE  

Atherosclerosis 20121123 2


<h4>Background</h4>Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized.<h4>Methods</h4>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 f  ...[more]

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