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; Marie N Harder; Kasper Pilgaard; Charlotta Pisinger; Alena Stancáková; Johanna Kuusisto; Niels Grarup; Kristine Færch; Pernille Poulsen; Daniel R Witte; Torben Jørgensen; Allan Vaag; Markku Laakso; Oluf Pedersen; Torben Hansen

doi:10.1371/journal.pone.0027096

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

8 Citations (Scopus)

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.

Original language	English
Journal	P L o S One
Volume	6
Issue number	11
Pages (from-to)	e27096
Number of pages	6
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0027096
Publication status	Published - 4 Nov 2011

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10.1371/journal.pone.0027096

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Andersson, E. A., Harder, M. N., Pilgaard, K., Pisinger, C., Stancáková, A., Kuusisto, J., Grarup, N., Færch, K., Poulsen, P., Witte, D. R., Jørgensen, T., Vaag, A., Laakso, M., Pedersen, O., & Hansen, T. (2011). The Birth Weight Lowering C-Allele of rs900400 Near LEKR1 and CCNL1 Associates with Elevated Insulin Release following an Oral Glucose Challenge. P L o S One, 6(11), e27096. https://doi.org/10.1371/journal.pone.0027096

Andersson, EA, Harder, MN, Pilgaard, K, Pisinger, C, Stancáková, A, Kuusisto, J, Grarup, N , Færch, K, Poulsen, P, Witte, DR, Jørgensen, T, Vaag, A, Laakso, M, Pedersen, O & Hansen, T 2011, 'The Birth Weight Lowering C-Allele of rs900400 Near LEKR1 and CCNL1 Associates with Elevated Insulin Release following an Oral Glucose Challenge', P L o S One, vol. 6, no. 11, pp. e27096. https://doi.org/10.1371/journal.pone.0027096

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title = "The Birth Weight Lowering C-Allele of rs900400 Near LEKR1 and CCNL1 Associates with Elevated Insulin Release following an Oral Glucose Challenge",

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.",

author = "Andersson, {Ehm A} and Harder, {Marie N} and Kasper Pilgaard and Charlotta Pisinger and Alena Stanc{\'a}kov{\'a} and Johanna Kuusisto and Niels Grarup and Kristine F{\ae}rch and Pernille Poulsen and Witte, {Daniel R} and Torben J{\o}rgensen and Allan Vaag and Markku Laakso and Oluf Pedersen and Torben Hansen",

year = "2011",

month = nov,

day = "4",

doi = "10.1371/journal.pone.0027096",

language = "English",

volume = "6",

pages = "e27096",

journal = "P L o S One",

issn = "1932-6203",

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TY - JOUR

T1 - The Birth Weight Lowering C-Allele of rs900400 Near LEKR1 and CCNL1 Associates with Elevated Insulin Release following an Oral Glucose Challenge

AU - Andersson, Ehm A

AU - Harder, Marie N

AU - Pilgaard, Kasper

AU - Pisinger, Charlotta

AU - Stancáková, Alena

AU - Kuusisto, Johanna

AU - Grarup, Niels

AU - Færch, Kristine

AU - Poulsen, Pernille

AU - Witte, Daniel R

AU - Jørgensen, Torben

AU - Vaag, Allan

AU - Laakso, Markku

AU - Pedersen, Oluf

AU - Hansen, Torben

PY - 2011/11/4

Y1 - 2011/11/4

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0027096

DO - 10.1371/journal.pone.0027096

M3 - Journal article

C2 - 22073261

SN - 1932-6203

VL - 6

SP - e27096

JO - P L o S One

JF - P L o S One

IS - 11

ER -

The Birth Weight Lowering C-Allele of rs900400 Near LEKR1 and CCNL1 Associates with Elevated Insulin Release following an Oral Glucose Challenge

Abstract

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