Interaction between prenatal growth and high-risk genotypes in the development of type 2 diabetes
Interaction between prenatal growth and high-risk genotypes in the development of type 2 diabetes
Aims/hypothesis: early environmental factors and genetic variants have been reported to be involved in the pathogenesis of type 2 diabetes. The aim of this study was to investigate whether there is an interaction between birthweight and common variants in the TCF7L2, HHEX, PPARG, KCNJ11, SLC30A8, IGF2BP2, CDKAL1, CDKN2A/2B and JAZF1 genes in the risk of developing type 2 diabetes.
Methods: a total of 2,003 participants from the Helsinki Birth Cohort Study, 311 of whom were diagnosed with type 2 diabetes by an OGTT, were genotyped for the specified variants. Indices for insulin sensitivity and secretion were calculated.
Results: low birthweight was associated with type 2 diabetes (p?=?0.008) and impaired insulin secretion (p?=?0.04). Of the tested variants, the risk variant in HHEX showed a trend towards a low birthweight (p?=?0.09) and the risk variant in the CDKN2A/2B locus was associated with high birthweight (p?=?0.01). The TCF7L2 risk allele was associated with increased risk of type 2 diabetes. Pooling across all nine genes, each risk allele increased the risk of type 2 diabetes by 11%. Risk variants in the HHEX, CDKN2A/2B and JAZF1 genes interacted with birthweight, so that the risk of type 2 diabetes was highest in those with lower birthweight (p???0.05). The interaction was also present in the pooled data.
Conclusions/interpretation: low birthweight might affect the strength of the association of some common variants (HHEX, CDKN2A/2B and JAZF1) with type 2 diabetes. These findings need to be replicated in independent cohorts
genetic variants, interaction, prenatal growth, type 2 diabetes
825-829
Pulizzi, N.
61754595-d458-4917-80b4-115c2db81fc1
Lyssenko, V.
746e53ee-8e18-4b3b-b48d-3f2559c454f3
Jonsson, A.
5ba815f0-a29f-4c55-a2aa-293d4926da54
Osmond, C.
2677bf85-494f-4a78-adf8-580e1b8acb81
Laakso, M.
ec6734f9-b924-430e-89a0-47fa5c66110d
Kajantie, E.
d4e32f85-9988-4b83-b353-012210ea0151
Barker, D.J.
cabc3433-b628-43e5-9fd7-e6ff5769bf44
Groop, L.C.
16c6f961-f687-4478-90ce-0aca1fc62428
Eriksson, J.G.
eda300d2-b247-479f-95b9-f12d2c72e92b
May 2009
Pulizzi, N.
61754595-d458-4917-80b4-115c2db81fc1
Lyssenko, V.
746e53ee-8e18-4b3b-b48d-3f2559c454f3
Jonsson, A.
5ba815f0-a29f-4c55-a2aa-293d4926da54
Osmond, C.
2677bf85-494f-4a78-adf8-580e1b8acb81
Laakso, M.
ec6734f9-b924-430e-89a0-47fa5c66110d
Kajantie, E.
d4e32f85-9988-4b83-b353-012210ea0151
Barker, D.J.
cabc3433-b628-43e5-9fd7-e6ff5769bf44
Groop, L.C.
16c6f961-f687-4478-90ce-0aca1fc62428
Eriksson, J.G.
eda300d2-b247-479f-95b9-f12d2c72e92b
Pulizzi, N., Lyssenko, V., Jonsson, A., Osmond, C., Laakso, M., Kajantie, E., Barker, D.J., Groop, L.C. and Eriksson, J.G.
(2009)
Interaction between prenatal growth and high-risk genotypes in the development of type 2 diabetes.
Diabetologia, 52 (5), .
(doi:10.1007/s00125-009-1291-1).
Abstract
Aims/hypothesis: early environmental factors and genetic variants have been reported to be involved in the pathogenesis of type 2 diabetes. The aim of this study was to investigate whether there is an interaction between birthweight and common variants in the TCF7L2, HHEX, PPARG, KCNJ11, SLC30A8, IGF2BP2, CDKAL1, CDKN2A/2B and JAZF1 genes in the risk of developing type 2 diabetes.
Methods: a total of 2,003 participants from the Helsinki Birth Cohort Study, 311 of whom were diagnosed with type 2 diabetes by an OGTT, were genotyped for the specified variants. Indices for insulin sensitivity and secretion were calculated.
Results: low birthweight was associated with type 2 diabetes (p?=?0.008) and impaired insulin secretion (p?=?0.04). Of the tested variants, the risk variant in HHEX showed a trend towards a low birthweight (p?=?0.09) and the risk variant in the CDKN2A/2B locus was associated with high birthweight (p?=?0.01). The TCF7L2 risk allele was associated with increased risk of type 2 diabetes. Pooling across all nine genes, each risk allele increased the risk of type 2 diabetes by 11%. Risk variants in the HHEX, CDKN2A/2B and JAZF1 genes interacted with birthweight, so that the risk of type 2 diabetes was highest in those with lower birthweight (p???0.05). The interaction was also present in the pooled data.
Conclusions/interpretation: low birthweight might affect the strength of the association of some common variants (HHEX, CDKN2A/2B and JAZF1) with type 2 diabetes. These findings need to be replicated in independent cohorts
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More information
Published date: May 2009
Keywords:
genetic variants, interaction, prenatal growth, type 2 diabetes
Organisations:
Dev Origins of Health & Disease
Identifiers
Local EPrints ID: 68993
URI: http://eprints.soton.ac.uk/id/eprint/68993
ISSN: 0012-186X
PURE UUID: f622283a-49dd-4873-aaa1-fd9464900655
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Date deposited: 14 Oct 2009
Last modified: 14 Mar 2024 02:38
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Contributors
Author:
N. Pulizzi
Author:
V. Lyssenko
Author:
A. Jonsson
Author:
M. Laakso
Author:
E. Kajantie
Author:
D.J. Barker
Author:
L.C. Groop
Author:
J.G. Eriksson
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