ADCY5、ADRA2A、CDKAL1、CDKN2A/B、GRB10和TCF7L2基因内部或附近的风险等位基因会提高出生时及幼儿期的血糖水平：来自家族研究的结果。
Risk Alleles in/near ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2 Elevate Plasma Glucose Levels at Birth and in Early Childhood: Results from the FAMILY Study.
作者信息
Sohani Zahra N, Anand Sonia S, Robiou-du-Pont Sebastien, Morrison Katherine M, McDonald Sarah D, Atkinson Stephanie A, Teo Koon K, Meyre David
机构信息
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
出版信息
PLoS One. 2016 Apr 6;11(4):e0152107. doi: 10.1371/journal.pone.0152107. eCollection 2016.
BACKGROUND
Metabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood.
OBJECTIVES
We investigate whether common genetic variants identified in adults have an effect on glucose in early life.
METHODS
610 newborns, 463 mothers, and 366 fathers were included in the present study. Plasma glucose and anthropometric characteristics were collected at birth, 3, and 5 years. After quality assessment, 37 SNPs, which have demonstrated an association with fasting plasma glucose at the genome-wide threshold in adults, were studied. Quantitative trait disequilibrium tests and mixed-effects regressions were conducted to estimate an effect of the SNPs on glucose.
RESULTS
Risk alleles for 6 loci increased glucose levels from birth to 5 years of age (ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2, 4.85x10-3 ≤ P ≤ 4.60x10-2). Together, these 6 SNPs increase glucose by 0.05 mmol/L for each risk allele in a genotype score (P = 6.33x10-5). None of the associations described in the present study have been reported previously in early childhood.
CONCLUSION
Our data support the notion that a subset of loci contributing to plasma glucose variation in adults has an effect at birth and in early life.
背景
导致2型糖尿病的代谢异常始于儿童早期。
目的
我们调查在成人中鉴定出的常见基因变异是否对生命早期的血糖有影响。
方法
本研究纳入了610名新生儿、463名母亲和366名父亲。在出生时、3岁和5岁时收集血浆葡萄糖和人体测量特征。经过质量评估后，研究了37个单核苷酸多态性（SNP），这些SNP在成人全基因组阈值下已显示与空腹血浆葡萄糖相关。进行了数量性状不平衡测试和混合效应回归，以估计SNP对葡萄糖的影响。
结果
6个基因座的风险等位基因从出生到5岁均会升高血糖水平（腺苷酸环化酶5型、肾上腺素能受体α2A、细胞周期蛋白依赖性激酶5调节亚基相关蛋白1、细胞周期蛋白依赖性激酶抑制剂2A/2B、生长因子受体结合蛋白10和转录因子7样蛋白2，4.85×10⁻³≤P≤4.60×10⁻²）。在基因型评分中，这6个SNP每增加一个风险等位基因，血糖就会升高0.05 mmol/L（P = 6.33×10⁻⁵）。本研究中描述的关联在儿童早期均未被报道过。
结论
我们的数据支持这样一种观点，即导致成人血浆葡萄糖变异的一部分基因座在出生时和生命早期就有影响。
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