Effects of genetic variants in ADCY5, GIPR, GCKR and VPS13C on early impairment of glucose and insulin metabolism in children.
Effects of genetic variants in ADCY5, GIPR, GCKR and VPS13C on early impairment of glucose and insulin metabolism in children.
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DOI：
10.1371/journal.pone.0022101
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Körner A
中科院分区：
文献类型：
--
作者：
Windholz J;Kovacs P;Tönjes A;Dittrich K;Blüher S;Kiess W;Stumvoll M;Körner A
最近的全基因组关联研究发现了影响成人空腹和2小时血糖和胰岛素水平的新的候选基因。我们研究了其中四个基因座（ADCY5、GIPR、GCKR和VPS13C）在儿童早期葡萄糖和胰岛素代谢障碍中的作用。我们对638名高加索儿童进行了详细的代谢测试，包括oGTT，并通过线性回归分析评估了与葡萄糖和胰岛素代谢（包括空腹血糖、胰岛素水平和胰岛素敏感性/分泌指数）的相关性（包括年龄、性别、BMI-SDS和青春期阶段），对四个变异（rs2877716、rs1260326、rs10423928、rs17271305）进行了基因分型。rs2877716主要等位基因C （ADCY5）与空腹血浆胰岛素降低（P = 0.008）、胰岛素峰值降低（P = 0.009）、QUICKI升高（P = 0.016）和Matsuda胰岛素敏感性指数升高（P = 0.013）相关。rs17271305 （VPS13C）名义上与2 h血糖相关（P = 0.009），但与任何胰岛素或胰岛素敏感性参数无关。我们发现GIPR和GCKR变异与葡萄糖和胰岛素代谢参数没有关联。没有一种变异与身高、腰宽比或BMI-SDS等人体测量特征相关，这就排除了与肥胖的潜在关联。我们关于肥胖儿童的数据表明，ADCY5基因变异在早期胰岛素代谢障碍中起作用，VPS13C基因变异在早期血糖稳态障碍中起作用。
Recent genome-wide association studies identified novel candidate genes for fasting and 2 h blood glucose and insulin levels in adults. We investigated the role of four of these loci (ADCY5, GIPR, GCKR and VPS13C) in early impairment of glucose and insulin metabolism in children. We genotyped four variants (rs2877716; rs1260326; rs10423928; rs17271305) in 638 Caucasian children with detailed metabolic testing including an oGTT and assessed associations with measures of glucose and insulin metabolism (including fasting blood glucose, insulin levels and insulin sensitivity/secretion indices) by linear regression analyses adjusted for age, sex, BMI-SDS and pubertal stage. The major allele (C) of rs2877716 (ADCY5) was nominally associated with decreased fasting plasma insulin (P = 0.008), peak insulin (P = 0.009) and increased QUICKI (P = 0.016) and Matsuda insulin sensitivity index (P = 0.013). rs17271305 (VPS13C) was nominally associated with 2 h blood glucose (P = 0.009), but not with any of the insulin or insulin sensitivity parameters. We found no association of the GIPR and GCKR variants with parameters of glucose and insulin metabolism. None of the variants correlated with anthropometric traits such as height, WHR or BMI-SDS, which excluded potential underlying associations with obesity. Our data on obese children indicate effects of genetic variation within ADCY5 in early impairment of insulin metabolism and VPS13C in early impairment of blood glucose homeostasis.
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DOI：
10.1152/ajpheart.00050.2009
发表时间：
2009-11-01
影响因子：
4.8
作者：
Hu, Che-Lin;Chandra, Rachna;Vatner, Dorothy E.
通讯作者：
Vatner, Dorothy E.
影响因子：
8.3
作者：
Ortiz-Capisano, M. Cecilia;Ortiz, Pablo A.;Beierwaltes, William H.
通讯作者：
Beierwaltes, William H.
影响因子：
5.8
作者：
Koerner, Antje;Berndt, Janin;Kovacs, Peter
通讯作者：
Kovacs, Peter
新的遗传基因座涉及禁食葡萄糖稳态及其对2型糖尿病风险的影响。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
7.7
作者：
Goran, MI;Gower, BA
通讯作者：
Gower, BA