A gene-centric study of common carotid artery remodelling

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 AguMika 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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)440-446
Number of pages7
JournalAtherosclerosis
Volume226
Issue number2
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Adventitia
Common Carotid Artery
Abdominal Aortic Aneurysm
Single Nucleotide Polymorphism
Genes
Proxy
Meta-Analysis
Genetic Phenomena
Carotid Intima-Media Thickness
Case-Control Studies
Atherosclerosis
Cohort Studies
Chromosomes
Alleles
Vascular Remodeling
Proteins

Keywords

  • Abdominal aortic aneurysm
  • Carotid artery
  • Genome-wide association studies
  • Vascular remodelling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Harrison, S. C., Zabaneh, D., Asselbergs, F. W., Drenos, F., Jones, G. T., Shah, S., ... Humphries, S. E. (2013). A gene-centric study of common carotid artery remodelling. Atherosclerosis, 226(2), 440-446. https://doi.org/10.1016/j.atherosclerosis.2012.11.002

A gene-centric study of common carotid artery remodelling. / Harrison, Seamus C.; Zabaneh, Delilah; Asselbergs, Folkert W.; Drenos, Fotios; Jones, Gregory T.; Shah, Sonia; Gertow, Karl; Sennblad, Bengt; Strawbridge, Rona J.; Gigante, Bruna; Holewijn, Suzanne; De Graaf, Jacqueline; Vermeulen, Sita; Folkersen, Lasse; van Rij, Andre M.; Baldassarre, Damiano; Veglia, Fabrizio; Talmud, Philippa J.; Deanfield, John E.; Agu, Obi; Kivimaki, Mika; Kumari, Meena; Bown, Matthew J.; Nyyssönen, Kristiina; Rauramaa, Rainer; Smit, Andries J.; Franco-Cereceda, Anders; Giral, Philippe; Mannarino, Elmo; Silveira, Angela; Syvänen, Ann Christine; de Borst, Gert J.; van der Graaf, Yolanda; de Faire, Ulf; Baas, Annette F.; Blankensteijn, Jan D.; Wareham, Nicholas J.; Fowkes, Gerry; Tzoulaki, Ionna; Price, Jacqueline F.; Tremoli, Elena; Hingorani, Aroon D.; Eriksson, Per; Hamsten, Anders; Humphries, Steve E.

In: Atherosclerosis, Vol. 226, No. 2, 02.2013, p. 440-446.

Research output: Contribution to journalArticle

Harrison, SC, Zabaneh, D, Asselbergs, FW, Drenos, F, Jones, GT, Shah, S, Gertow, K, Sennblad, B, Strawbridge, RJ, Gigante, B, Holewijn, S, De Graaf, J, Vermeulen, S, Folkersen, L, van Rij, AM, Baldassarre, D, Veglia, F, Talmud, PJ, Deanfield, JE, Agu, O, Kivimaki, M, Kumari, M, Bown, MJ, Nyyssönen, K, Rauramaa, R, Smit, AJ, Franco-Cereceda, A, Giral, P, Mannarino, E, Silveira, A, Syvänen, AC, de Borst, GJ, van der Graaf, Y, de Faire, U, Baas, AF, Blankensteijn, JD, Wareham, NJ, Fowkes, G, Tzoulaki, I, Price, JF, Tremoli, E, Hingorani, AD, Eriksson, P, Hamsten, A & Humphries, SE 2013, 'A gene-centric study of common carotid artery remodelling', Atherosclerosis, vol. 226, no. 2, pp. 440-446. https://doi.org/10.1016/j.atherosclerosis.2012.11.002
Harrison SC, Zabaneh D, Asselbergs FW, Drenos F, Jones GT, Shah S et al. A gene-centric study of common carotid artery remodelling. Atherosclerosis. 2013 Feb;226(2):440-446. https://doi.org/10.1016/j.atherosclerosis.2012.11.002
Harrison, Seamus C. ; Zabaneh, Delilah ; Asselbergs, Folkert W. ; Drenos, Fotios ; Jones, Gregory T. ; Shah, Sonia ; Gertow, Karl ; Sennblad, Bengt ; Strawbridge, Rona J. ; Gigante, Bruna ; Holewijn, Suzanne ; De Graaf, Jacqueline ; Vermeulen, Sita ; Folkersen, Lasse ; van Rij, Andre M. ; Baldassarre, Damiano ; Veglia, Fabrizio ; Talmud, Philippa J. ; Deanfield, John E. ; Agu, Obi ; Kivimaki, Mika ; Kumari, Meena ; Bown, Matthew J. ; Nyyssönen, Kristiina ; Rauramaa, Rainer ; Smit, Andries J. ; Franco-Cereceda, Anders ; Giral, Philippe ; Mannarino, Elmo ; Silveira, Angela ; Syvänen, Ann Christine ; de Borst, Gert J. ; van der Graaf, Yolanda ; de Faire, Ulf ; Baas, Annette F. ; Blankensteijn, Jan D. ; Wareham, Nicholas J. ; Fowkes, Gerry ; Tzoulaki, Ionna ; Price, Jacqueline F. ; Tremoli, Elena ; Hingorani, Aroon D. ; Eriksson, Per ; Hamsten, Anders ; Humphries, Steve E. / A gene-centric study of common carotid artery remodelling. In: Atherosclerosis. 2013 ; Vol. 226, No. 2. pp. 440-446.
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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.",
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TY - JOUR

T1 - A gene-centric study of common carotid artery remodelling

AU - Harrison, Seamus C.

AU - Zabaneh, Delilah

AU - Asselbergs, Folkert W.

AU - Drenos, Fotios

AU - Jones, Gregory T.

AU - Shah, Sonia

AU - Gertow, Karl

AU - Sennblad, Bengt

AU - Strawbridge, Rona J.

AU - Gigante, Bruna

AU - Holewijn, Suzanne

AU - De Graaf, Jacqueline

AU - Vermeulen, Sita

AU - Folkersen, Lasse

AU - van Rij, Andre M.

AU - Baldassarre, Damiano

AU - Veglia, Fabrizio

AU - Talmud, Philippa J.

AU - Deanfield, John E.

AU - Agu, Obi

AU - Kivimaki, Mika

AU - Kumari, Meena

AU - Bown, Matthew J.

AU - Nyyssönen, Kristiina

AU - Rauramaa, Rainer

AU - Smit, Andries J.

AU - Franco-Cereceda, Anders

AU - Giral, Philippe

AU - Mannarino, Elmo

AU - Silveira, Angela

AU - Syvänen, Ann Christine

AU - de Borst, Gert J.

AU - van der Graaf, Yolanda

AU - de Faire, Ulf

AU - Baas, Annette F.

AU - Blankensteijn, Jan D.

AU - Wareham, Nicholas J.

AU - Fowkes, Gerry

AU - Tzoulaki, Ionna

AU - Price, Jacqueline F.

AU - Tremoli, Elena

AU - Hingorani, Aroon D.

AU - Eriksson, Per

AU - Hamsten, Anders

AU - Humphries, Steve E.

PY - 2013/2

Y1 - 2013/2

N2 - 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.

AB - 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.

KW - Abdominal aortic aneurysm

KW - Carotid artery

KW - Genome-wide association studies

KW - Vascular remodelling

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