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Interaction between prenatal growth and high-risk genotypes in the development of type 2 diabetes

Pulizzi, N.; Lyssenko, Valeriya LU ; Jonsson, Anna LU ; Osmond, C.; Laakso, M.; Kajantie, E.; Barker, D. J.; Groop, Leif LU and Eriksson, J. G. (2009) In Diabetologia 52(5). p.825-829
Abstract
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. 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. 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... (More)
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. 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. 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 a parts per thousand currency signaEuro parts per thousand 0.05). The interaction was also present in the pooled data. 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Type 2 diabetes, Prenatal growth, Genetic variants, Interaction
in
Diabetologia
volume
52
issue
5
pages
825 - 829
publisher
Springer Verlag
external identifiers
  • wos:000264884100013
  • scopus:64149117551
ISSN
1432-0428
DOI
10.1007/s00125-009-1291-1
language
English
LU publication?
yes
id
44e5b134-e549-43b0-88f7-5629ec504dab (old id 1400690)
date added to LUP
2009-06-15 13:25:54
date last changed
2017-08-06 03:47:29
@article{44e5b134-e549-43b0-88f7-5629ec504dab,
  abstract     = {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. 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. 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 a parts per thousand currency signaEuro parts per thousand 0.05). The interaction was also present in the pooled data. 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.},
  author       = {Pulizzi, N. and Lyssenko, Valeriya and Jonsson, Anna and Osmond, C. and Laakso, M. and Kajantie, E. and Barker, D. J. and Groop, Leif and Eriksson, J. G.},
  issn         = {1432-0428},
  keyword      = {Type 2 diabetes,Prenatal growth,Genetic variants,Interaction},
  language     = {eng},
  number       = {5},
  pages        = {825--829},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Interaction between prenatal growth and high-risk genotypes in the development of type 2 diabetes},
  url          = {http://dx.doi.org/10.1007/s00125-009-1291-1},
  volume       = {52},
  year         = {2009},
}