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DNA methylation at birth within the promoter of ANRIL predicts markers of cardiovascular risk at 9 years

DNA methylation at birth within the promoter of ANRIL predicts markers of cardiovascular risk at 9 years
DNA methylation at birth within the promoter of ANRIL predicts markers of cardiovascular risk at 9 years
Aims: Antisense non-coding RNA in the INK4 locus (ANRIL) fixed genetic variants have consistently been linked with coronary heart disease (CHD) risk. We investigated relationships between perinatal ANRIL promoter DNA methylation and CHD risk markers in children aged 9 years. Genetic variants in the non-coding RNA ANRIL identify it as an important CHD risk locus. Increasing evidence suggests that the early life environment may act through epigenetic processes to influence later CHD risk markers such as increased arterial pulse wave velocity (PWV, a measure of arterial stiffness) blood pressure or heart rate.

Methods and results: Using pyrosequencing, ANRIL DNA methylation at nine CpG sites was measured in the umbilical cord from 144 children in a UK mother-offspring cohort and related to the descending aorta PWV measured by velocity-encoded phase contrast MRI at age 9 years. Perinatal methylation was not associated with child’s later blood pressure, but higher methylation at CpG5 was associated with increased childhood PWV (??=?0.066 m/s/10 % methylation increase [95 % CI, 0.004 to 0.128], p?=?0.037); 10 % decreases in methylation at CpG1 and CpG2 were associated with increased heart rate (CpG1 ??=?1.93 [0.07 to 3.8] beats/min, p?=?0.041; CpG2 ??=?2.30 [0.18 to 4.41] beats/min, p?=?0.033, accounting for potential confounding variables). The associations with perinatal ANRIL promoter methylation were independent of neighbouring fixed genetic variants.

Conclusions: Our findings suggest developmental epigenetic regulation of ANRIL promoter methylation as a factor in later CHD risk in children.
1868-7075
1-6
Murray, Robert
c3e973b5-525c-49b3-96ee-af60a666a0f4
Bryant, Jennifer
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Titcombe, Philip
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Barton, Sheila
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Inskip, Hazel
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Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Hanson, Mark
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Godfrey, Keith
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Murray, Robert
c3e973b5-525c-49b3-96ee-af60a666a0f4
Bryant, Jennifer
f4aeabbf-5014-45ed-bab4-e041d55afb88
Titcombe, Philip
a84c9fad-0580-42f9-8bb6-db0fe20435aa
Barton, Sheila
4f674382-ca0b-44ad-9670-e71a0b134ef0
Inskip, Hazel
5fb4470a-9379-49b2-a533-9da8e61058b7
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Hanson, Mark
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Godfrey, Keith
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd

Murray, Robert, Bryant, Jennifer, Titcombe, Philip, Barton, Sheila, Inskip, Hazel, Harvey, Nicholas, Cooper, Cyrus, Lillycrop, Karen, Hanson, Mark and Godfrey, Keith (2016) DNA methylation at birth within the promoter of ANRIL predicts markers of cardiovascular risk at 9 years. Clinical Epigenetics, 8 (90), 1-6. (doi:10.1186/s13148-016-0259-5). (PMID:27594927)

Record type: Article

Abstract

Aims: Antisense non-coding RNA in the INK4 locus (ANRIL) fixed genetic variants have consistently been linked with coronary heart disease (CHD) risk. We investigated relationships between perinatal ANRIL promoter DNA methylation and CHD risk markers in children aged 9 years. Genetic variants in the non-coding RNA ANRIL identify it as an important CHD risk locus. Increasing evidence suggests that the early life environment may act through epigenetic processes to influence later CHD risk markers such as increased arterial pulse wave velocity (PWV, a measure of arterial stiffness) blood pressure or heart rate.

Methods and results: Using pyrosequencing, ANRIL DNA methylation at nine CpG sites was measured in the umbilical cord from 144 children in a UK mother-offspring cohort and related to the descending aorta PWV measured by velocity-encoded phase contrast MRI at age 9 years. Perinatal methylation was not associated with child’s later blood pressure, but higher methylation at CpG5 was associated with increased childhood PWV (??=?0.066 m/s/10 % methylation increase [95 % CI, 0.004 to 0.128], p?=?0.037); 10 % decreases in methylation at CpG1 and CpG2 were associated with increased heart rate (CpG1 ??=?1.93 [0.07 to 3.8] beats/min, p?=?0.041; CpG2 ??=?2.30 [0.18 to 4.41] beats/min, p?=?0.033, accounting for potential confounding variables). The associations with perinatal ANRIL promoter methylation were independent of neighbouring fixed genetic variants.

Conclusions: Our findings suggest developmental epigenetic regulation of ANRIL promoter methylation as a factor in later CHD risk in children.

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Accepted/In Press date: 24 August 2016
e-pub ahead of print date: 2 September 2016
Published date: 2 September 2016
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 400152
URI: http://eprints.soton.ac.uk/id/eprint/400152
ISSN: 1868-7075
PURE UUID: 7ffe8dea-1c93-4304-b13c-262d99b8687f
ORCID for Philip Titcombe: ORCID iD orcid.org/0000-0002-7797-8571
ORCID for Sheila Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for Hazel Inskip: ORCID iD orcid.org/0000-0001-8897-1749
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Karen Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Mark Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618

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Date deposited: 12 Sep 2016 13:50
Last modified: 17 Dec 2019 02:01

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Contributors

Author: Robert Murray
Author: Jennifer Bryant
Author: Philip Titcombe ORCID iD
Author: Sheila Barton ORCID iD
Author: Hazel Inskip ORCID iD
Author: Nicholas Harvey ORCID iD
Author: Cyrus Cooper ORCID iD
Author: Karen Lillycrop ORCID iD
Author: Mark Hanson ORCID iD
Author: Keith Godfrey ORCID iD

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