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 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

doi:10.1016/j.atherosclerosis.2012.11.002

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 journal › Article (Academic Journal) › peer-review

6 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, 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.

Original language	English
Pages (from-to)	440-6
Number of pages	7
Journal	Atherosclerosis
Volume	226
Issue number	2
DOIs	https://doi.org/10.1016/j.atherosclerosis.2012.11.002
Publication status	Published - Feb 2013

Keywords

Aged
Aortic Aneurysm, Abdominal
Carotid Artery, Common
Carotid Intima-Media Thickness
Chromosomes, Human, Pair 1
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Phenotype
Polymorphism, Single Nucleotide
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.atherosclerosis.2012.11.002

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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., ... Humphries, S. E. (2013). A gene-centric study of common carotid artery remodelling. Atherosclerosis, 226(2), 440-6. https://doi.org/10.1016/j.atherosclerosis.2012.11.002

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title = "A gene-centric study of common carotid artery remodelling",

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, 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.",

keywords = "Aged, Aortic Aneurysm, Abdominal, Carotid Artery, Common, Carotid Intima-Media Thickness, Chromosomes, Human, Pair 1, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't",

author = "Harrison, {Seamus C} and Delilah Zabaneh and Asselbergs, {Folkert W} and Fotios Drenos and Jones, {Gregory T} and Sonia Shah and Karl Gertow and Bengt Sennblad and Strawbridge, {Rona J} and Bruna Gigante and Suzanne Holewijn and {De Graaf}, Jacqueline and Sita Vermeulen and Lasse Folkersen and {van Rij}, {Andre M} and Damiano Baldassarre and Fabrizio Veglia and Talmud, {Philippa J} and Deanfield, {John E} and Obi Agu and Mika Kivimaki and Meena Kumari and Bown, {Matthew J} and Kristiina Nyyss{\"o}nen and Rainer Rauramaa and Smit, {Andries J} and Anders Franco-Cereceda and Philippe Giral and Elmo Mannarino and Angela Silveira and Ann-Christine Syv{\"a}nen and {de Borst}, {Gert J} and {van der Graaf}, Yolanda and {de Faire}, Ulf and Baas, {Annette F} and Blankensteijn, {Jan D} and Wareham, {Nicholas J} and Gerry Fowkes and Ionna Tzoulaki and Price, {Jacqueline F} and Elena Tremoli and Hingorani, {Aroon D} and Per Eriksson and Anders Hamsten and Humphries, {Steve E}",

year = "2013",

month = feb,

doi = "10.1016/j.atherosclerosis.2012.11.002",

language = "English",

volume = "226",

pages = "440--6",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier",

number = "2",

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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, A-C, 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. 440-6. https://doi.org/10.1016/j.atherosclerosis.2012.11.002

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, 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.

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, 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.

KW - Aged

KW - Aortic Aneurysm, Abdominal

KW - Carotid Artery, Common

KW - Carotid Intima-Media Thickness

KW - Chromosomes, Human, Pair 1

KW - Female

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Middle Aged

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Journal Article

KW - Meta-Analysis

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.atherosclerosis.2012.11.002

DO - 10.1016/j.atherosclerosis.2012.11.002

M3 - Article (Academic Journal)

C2 - 23246012

SN - 0021-9150

VL - 226

SP - 440

EP - 446

JO - Atherosclerosis

JF - Atherosclerosis

IS - 2

ER -

A gene-centric study of common carotid artery remodelling

Abstract

Keywords

UN SDGs

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