儿童血糖相关的基因位点
  • 纳入307名5岁的儿童,随访其整个儿童期,检测其基因组中121个核苷酸多态性位点(SNPs);
  • 筛选出与血糖变化、胰岛素抵抗相关的基因位点包括:rs780094、 rs4457053、rs11257655, rs12779790、rs1111875, rs7178572、 rs9787485、rs1535500等;
  • 其中一些位点与年龄、性别、生长激素等因素存在交互作用;
  • 基因是独立于BMI因素外的儿童期糖尿病发生的重要影响因素之一;
  • 当儿童发生血糖增高时,胰岛B细胞的损伤早于胰岛素抵抗的出现。
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小笋干儿
本研究利用人群资料,通过核苷酸多态性检测和筛选,识别出诸多与儿童血糖增高可能相关的基因位点,为进一步研究基因-环境交互作用提供了基础。
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Diabetes Care [IF:15.27]

Genetic Susceptibility Determines β-Cell Function and Fasting Glycemia Trajectories Throughout Childhood: A 12-Year Cohort Study (EarlyBird 76)

儿童期空腹血糖变化、胰岛B细胞功能相关的基因易感性:12年的队列研究

10.2337/dc19-0806

01-08, Article

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OBJECTIVE: Previous studies suggested that childhood prediabetes might develop prior to obesity and be associated with relative insulin deficiency. We proposed that the insulin-deficient phenotype is genetically determined and tested this hypothesis by longitudinal modeling of insulin and glucose traits with diabetes risk genotypes in the EarlyBird cohort.
RESEARCH DESIGN AND METHODS: EarlyBird is a nonintervention prospective cohort study that recruited 307 healthy U.K. children at 5 years of age and followed them throughout childhood. We genotyped 121 single nucleotide polymorphisms (SNPs) previously associated with diabetes risk, identified in the adult population. Association of SNPs with fasting insulin and glucose and HOMA indices of insulin resistance and β-cell function, available from 5 to 16 years of age, were tested. Association analysis with hormones was performed on selected SNPs.
RESULTS: Several candidate loci influenced the course of glycemic and insulin traits, including rs780094 (GCKR), rs4457053 (ZBED3), rs11257655 (CDC123), rs12779790 (CDC123 and CAMK1D), rs1111875 (HHEX), rs7178572 (HMG20A), rs9787485 (NRG3), and rs1535500 (KCNK16). Some of these SNPs interacted with age, the growth hormone-IGF-1 axis, and adrenal and sex steroid activity.
CONCLUSIONS: The findings that genetic markers influence both elevated and average courses of glycemic traits and β-cell function in children during puberty independently of BMI are a significant step toward early identification of children at risk for diabetes. These findings build on our previous observations that pancreatic β-cell defects predate insulin resistance in the onset of prediabetes. Understanding the mechanisms of interactions among genetic factors, puberty, and weight gain would allow the development of new and earlier disease-management strategies in children.

First Authors:
Jerome Carayol

Correspondence Authors:
Jerome Carayol,Francois-Pierre Martin

All Authors:
Jerome Carayol,Joanne Hosking,Jonathan Pinkney,Julien Marquis,Aline Charpagne,Sylviane Metairon,Alison Jeffery,Jörg Hager,Francois-Pierre Martin

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