Document Detail

A gene-centric study of common carotid artery remodelling.
MedLine Citation:
PMID:  23246012     Owner:  NLM     Status:  MEDLINE    
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, 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.
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.
Seamus C Harrison; Delilah Zabaneh; Folkert W Asselbergs; Fotios Drenos; Gregory T Jones; Sonia Shah; Karl Gertow; Bengt Sennblad; Rona J Strawbridge; Bruna Gigante; Suzanne Holewijn; Jacqueline De Graaf; Sita Vermeulen; Lasse Folkersen; Andre M van Rij; Damiano Baldassarre; Fabrizio Veglia; Philippa J Talmud; John E Deanfield; Obi Agu; Mika Kivimaki; Meena Kumari; Matthew J Bown; Kristiina Nyyssönen; Rainer Rauramaa; Andries J Smit; Anders Franco-Cereceda; Philippe Giral; Elmo Mannarino; Angela Silveira; Ann-Christine Syvänen; Gert J de Borst; Yolanda van der Graaf; Ulf de Faire; Annette F Baas; Jan D Blankensteijn; Nicholas J Wareham; Gerry Fowkes; Ionna Tzoulaki; Jacqueline F Price; Elena Tremoli; Aroon D Hingorani; Per Eriksson; Anders Hamsten; Steve E Humphries
Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't     Date:  2012-11-23
Journal Detail:
Title:  Atherosclerosis     Volume:  226     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-15     Completed Date:  2013-07-18     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  440-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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MeSH Terms
Aortic Aneurysm, Abdominal / genetics*,  pathology
Carotid Artery, Common / pathology*
Carotid Intima-Media Thickness* / trends
Chromosomes, Human, Pair 1 / genetics
Genetic Association Studies / methods*
Genetic Predisposition to Disease
Middle Aged
Polymorphism, Single Nucleotide
Grant Support
CZB/4/672//Chief Scientist Office

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