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. 2011;6(11):e27096.
doi: 10.1371/journal.pone.0027096. Epub 2011 Nov 4.

The birth weight lowering C-allele of rs900400 near LEKR1 and CCNL1 associates with elevated insulin release following an oral glucose challenge

Ehm A Andersson  1 , Marie N Harder, Kasper Pilgaard, Charlotta Pisinger, Alena Stančáková, Johanna Kuusisto, Niels Grarup, Kristine Færch, Pernille Poulsen, Daniel R Witte, Torben Jørgensen, Allan Vaag, Markku Laakso, Oluf Pedersen, Torben Hansen
Affiliations

The birth weight lowering C-allele of rs900400 near LEKR1 and CCNL1 associates with elevated insulin release following an oral glucose challenge

Ehm A Andersson et al. PLoS One. 2011.

Abstract

Background and aim: The first genome-wide association study on birth weight was recently published and the most significant associated birth weight lowering variant was the rs900400 C-allele located near LEKR1 and CCNL1. We aimed to replicate the association with birth weight in the Danish Inter99 study and furthermore to evaluate associations between rs900400 and indices of insulin secretion and insulin sensitivity obtained by oral glucose tolerance tests in adults from the Danish Inter99 study and the Finnish, Metabolic Syndrome in Men (METSIM) sample.

Methods: For 4,744 of 6,784 Inter99 participants, midwife journals were traced through the Danish State Archives and association of rs900400 with birth weight was examined. Associations between rs900400 and fasting serum insulin, fasting plasma glucose, insulinogenic index, homeostasis model assessment of insulin resistance (HOMA-IR) and disposition index were studied in 5,484 Danish and 6,915 Finnish non-diabetic individuals and combined in meta-analyses.

Results: The C-allele of rs900400 was associated with a 22.1 g lower birth weight ([-41.3;-3.0], P = 0.024) per allele. Moreover, in combined analyses of the Danish Inter99 study and the Finnish METSIM study we found that the birth weight lowering allele was associated with increased insulin release measured by the insulinogenic index (β = 2.25% [0.59; 3.91], P = 0.008) and with an increased disposition index (β = 1.76% [0.04; 3.49], P = 0.05).

Conclusion: The birth weight lowering effect of the C-allele of rs900400 located near LEKR1 and CCNL1 was replicated in the Danish population. Furthermore the C-allele was associated with increased insulin response following oral glucose stimulation in a meta-analysis based on Danish and Finnish non-diabetic individuals.

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Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts; KF and DRW are employed by Steno Diabetes Center A/S, a research hospital working in the Danish National Health Service and owned by Novo Nordisk A/S and own shares in Novo Nordisk A/S. OP is employed by Hagedorn Research Institute, which is a basic research facility of Novo Nordisk and have employee shares in Novo Nordisk. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Meta-analysis of rs900400 and insulinogenic index including 11,916 individuals from the Inter99 and METSIM study.
Effect size estimates and standard errors are combined in a meta-analysis using the inverse variance method. The black diamond represents the combined change in insulinogenic index per C-allele. Effect size estimate (β) and P-value are presented for the combined analysis with 95% confidence interval in square brackets.
See this image and copyright information in PMC

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