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

På svenska

Author

  • N. Pulizzi
  • Valeriya Lyssenko
  • Anna Jonsson
  • C. Osmond
  • M. Laakso
  • E. Kajantie
  • D. J. Barker
  • Leif Groop
  • J. G. Eriksson

Summary, in English

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.

Publishing year

2009

Language

English

Pages

825-829

Publication/Series

Diabetologia

Volume

52

Issue

5

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • Type 2 diabetes
  • Prenatal growth
  • Genetic variants
  • Interaction

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1432-0428