Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
PLoS One. 2011;6(11):e27096. doi: 10.1371/journal.pone.0027096. Epub 2011 Nov 4.
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.
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.
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).
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.
最近发表了第一项关于出生体重的全基因组关联研究，最显著的与降低出生体重相关的变异是位于 LEKR1 和 CCNL1 附近的 rs900400C 等位基因。我们旨在复制丹麦 Inter99 研究中与出生体重的关联，并进一步评估 rs900400 与成年人口服葡萄糖耐量试验中胰岛素分泌和胰岛素敏感性指数之间的关联，这些参与者来自丹麦 Inter99 研究和芬兰代谢综合征男性（METSIM）样本。
在 Inter99 研究的 6784 名参与者中，有 4744 名参与者的助产士日志通过丹麦国家档案馆进行了追溯，并对 rs900400 与出生体重的关系进行了检查。在 5484 名丹麦和 6915 名芬兰非糖尿病个体中研究了 rs900400 与空腹血清胰岛素、空腹血浆葡萄糖、胰岛素生成指数、稳态模型评估的胰岛素抵抗（HOMA-IR）和处置指数之间的关系，并在荟萃分析中进行了合并。
rs900400 的 C 等位基因与每个等位基因低 22.1 克的出生体重相关[-41.3；-3.0]，P=0.024）。此外，在丹麦 Inter99 研究和芬兰 METSIM 研究的合并分析中，我们发现降低出生体重的等位基因与胰岛素生成指数测量的胰岛素释放增加有关（β=2.25%[0.59；3.91]，P=0.008），并且与处置指数增加有关（β=1.76%[0.04；3.49]，P=0.05）。
位于 LEKR1 和 CCNL1 附近的 rs900400C 等位基因降低出生体重的作用在丹麦人群中得到了复制。此外，在基于丹麦和芬兰非糖尿病个体的荟萃分析中，C 等位基因与口服葡萄糖刺激后的胰岛素反应增加有关。
