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. 2009 May;52(5):825-9.
doi: 10.1007/s00125-009-1291-1. Epub 2009 Feb 19.

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

N Pulizzi  1 , V Lyssenko, A Jonsson, C Osmond, M Laakso, E Kajantie, D J Barker, L C Groop, J G Eriksson
Affiliations

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

N Pulizzi et al. Diabetologia. 2009 May.

Erratum in

  • Diabetologia. 2009 Dec;52(12):2671-2

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 14%. [corrected] 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 <or= 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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