Top Single Nucleotide Polymorphisms Affecting Carbohydrate Metabolism in Metabolic Syndrome: From the LIPGENE Study
Top Single Nucleotide Polymorphisms Affecting Carbohydrate Metabolism in Metabolic Syndrome: From the LIPGENE Study
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DOI：
10.1210/jc.2013-3165
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发表时间：
2014-02-01
影响因子：
5.8
通讯作者：
Lopez-Miranda, Jose
中科院分区：
文献类型：
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作者：
Delgado-Lista, Javier;Perez-Martinez, Pablo;Lopez-Miranda, Jose
基本原理：代谢综合征（MetS）是一种以能量代谢改变、胰岛素抵抗和心血管风险升高为特征的高患病率疾病。目的：尽管许多单核苷酸多态性（SNPs）与某些MetS特征相关，但分析SNPs对MetS中碳水化合物代谢影响的研究很少。904个SNPs通过在LIPGENE研究的450名参与者中进行静脉内葡萄糖耐量试验，测试了标签SNP和功能SNP对8种空腹和碳水化合物代谢动态标志物的影响。从382个SNP和任何表型变量之间的初始基因-表型关联中，61个（预选变量的16%）在自举后仍然显着。影响糖代谢变量的主要SNP如下：空腹血糖，rs 26125（PPARGC 1B）;空腹胰岛素，rs 4759277（LRP 1）; C肽，rs 4759277（LRP 1）;胰岛素抵抗的稳态评估，rs 4759277（LRP 1）;定量胰岛素敏感性检查指数，rs 184003（AGER）;敏感性指数rs7301876（ABCC 9）、急性胰岛素对葡萄糖的反应rs 290481（TCF 7 L2）和处置指数rs 12691（CEBPA）。我们在这里描述了450例空腹和餐后样本中大约1000个候选基因变异中与碳水化合物代谢表型特征相关的最高SNPs。来自LIPGENE研究的MetS患者。
Rationale: Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk.Objectives: Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS.Methods: A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study.Findings: From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA).Conclusions: We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.