Else Kroener-Fresenius-Centre for Nutritional Medicine, University Hospital Klinikum rechts der Isar, Universität München, Munich, Germany.
Eur J Endocrinol. 2011 Feb;164(2):205-12. doi: 10.1530/EJE-10-0588. Epub 2010 Nov 8.
Genome-wide association studies have shown that the melatonin receptor 1B (MTNR1B) gene locus is strongly associated with fasting glucose and β-cell function. However, data are rather limited to the adult population and normal-weight children. So far, little is known whether similar associations are present in overweight and obese children and adolescents.
The aim is to investigate an MTNR1B polymorphism in a sample of 310 overweight and obese children and adolescents (mean body mass index standard deviation score (BMI-SDS)): 2.74 (± 0.55), mean age: 14 (± 2) years), who participated in a short-term weight-loss program based on energy reduction, physical activity, and behavior therapy.
We investigated an association between genotype and fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and of β-cell function (HOMA-B), and anthropometric parameters and their change during intervention.
The minor G allele of polymorphism rs10830963 was significantly associated with increased fasting glucose (0.205 mmol/l, P<0.0001) and decreased HOMA-B (-0.353, P < 0.0001). Categorizing the sample into BMI-SDS groups, these significant associations were abolished in children with BMI-SDS below 2.5 but remained in those with higher BMI-SDS values with stronger β-estimates. The P value for the genotype × BMI-SDS category interaction was 0.012 for fasting glucose and 0.083 for HOMA-B. There was no significant association between genotype and anthropometric parameters and their change during intervention.
This is the first single study, replicating the association between the MTNR1B locus and diabetes-related traits in overweight and obese children and adolescents. The effect sizes in children and adolescents seem to be stronger than in adults and differed among BMI-SDS categories.
全基因组关联研究表明，褪黑素受体 1B（MTNR1B）基因座与空腹血糖和β细胞功能密切相关。然而，数据主要局限于成年人群和体重正常的儿童。到目前为止，对于超重和肥胖的儿童和青少年中是否存在类似的关联知之甚少。
本研究旨在调查一个 MTNR1B 多态性在 310 例超重和肥胖儿童和青少年（平均体重指数标准差评分（BMI-SDS）：2.74（±0.55），平均年龄：14（±2）岁）中的情况，这些儿童和青少年参与了一个基于能量减少、体力活动和行为治疗的短期减肥计划。
我们调查了基因型与空腹血糖、空腹胰岛素、胰岛素抵抗稳态模型评估（HOMA-IR）和β细胞功能（HOMA-B）以及人体测量参数及其在干预过程中的变化之间的关联。
rs10830963 多态性的次要 G 等位基因与空腹血糖升高（0.205mmol/L，P<0.0001）和 HOMA-B 降低（-0.353，P<0.0001）显著相关。将样本分为 BMI-SDS 组后，BMI-SDS 低于 2.5 的儿童中这些显著相关性被消除，但在 BMI-SDS 值较高的儿童中仍存在，且β估计值更强。基因型与 BMI-SDS 类别之间的交互作用的 P 值在空腹血糖为 0.012，在 HOMA-B 为 0.083。基因型与干预过程中人体测量参数及其变化之间没有显著关联。
这是第一项在超重和肥胖儿童和青少年中复制 MTNR1B 基因座与糖尿病相关特征关联的单一研究。儿童和青少年中的效应大小似乎比成年人更强，并且在 BMI-SDS 类别之间存在差异。
