Variation in IGF2BP2 interacts with adiposity to alter insulin sensitivity in Mexican Americans.
Variation in IGF2BP2 interacts with adiposity to alter insulin sensitivity in Mexican Americans.
复制标题
DOI：
10.1038/oby.2008.593
复制
发表时间：
2009-04
期刊：
影响因子：
6.9
通讯作者：
Watanabe, Richard M.
中科院分区：
文献类型：
--
作者：
Li, Xia;Allayee, Hooman;Xiang, Anny H.;Trigo, Enrique;Hartiala, Jaana;Lawrence, Jean M.;Buchanan, Thomas A.;Watanabe, Richard M.
全基因组关联研究表明，胰岛素样生长因子 2 结合蛋白 2 (IGF2BP2) 的变异与 2 型糖尿病 (T2DM) 相关。我们检查了 BetaGene 研究中妊娠期糖尿病 (GDM) 先证者家庭中 IGF2BP2 的 20 kb 区域与 T2DM 相关数量性状的关联。我们对来自 146 个家族的 717 名个体的 14 个单核苷酸多态性 (SNP) 进行了基因分型，这些个体通过口服葡萄糖耐量试验 (OGTT)、静脉葡萄糖耐量试验 (IVGTT) 和最小模型分析以及双能 X 射线吸收测定法扫描体脂百分比进行表型分析。使用方差成分框架测试了捕获该区域大部分变异的 3 个 SNP 和 1 个 SNP 组合与 T2DM 相关数量性状的关联。经过多次测试校正后，rs11705701 显示与体脂百分比相关 (PACT = 0.041)，每个 A 等位基因拷贝体脂减少约 1.5–2%。接下来我们测试了 rs11705701 和体脂肪之间的相互作用是否与 T2DM 相关数量性状相关。 rs11705701 与胰岛素敏感性显着相关 (Bonferroni P = 0.028)，与 OGTT 2 小时胰岛素 (Bonferroni P = 0.066) 和处置指数 (DI) (Bonferroni P = 0.072) 略有相关。我们得出结论，IGF2BP2 中的 rs11705701 与体脂肪相关，这种对体脂肪的影响会影响胰岛素抵抗，从而可能导致 T2DM 风险。
Genome-wide association studies showed variation in insulin-like growth factor-2 binding protein 2 (IGF2BP2) to be associated with type 2 diabetes mellitus (T2DM). We examined a 20-kb region of IGF2BP2 for association with T2DM-related quantitative traits in Mexican American families of a proband with gestational diabetes mellitus (GDM) from the BetaGene study. We genotyped 14 single-nucleotide polymorphisms (SNPs) in 717 individuals from 146 families phenotyped by oral glucose tolerance test (OGTT), intravenous glucose tolerance tests (IVGTTs) with minimal model analysis, and dual-energy X-ray absorptiometry scan for percent body fat. Three SNPs and one SNP combination that captured the majority of the variation in the region were tested for association with T2DM-related quantitative traits using a variance components framework. After correction for multiple testing, rs11705701 showed association with percent body fat (PACT = 0.041) with body fat decreasing ∼1.5–2% per copy of the A allele. We next tested whether the interaction between rs11705701 and body fat was associated with T2DM-relative quantitative traits. rs11705701 was significantly associated with insulin sensitivity (Bonferroni P = 0.028) and marginally associated with OGTT 2-h insulin (Bonferroni P = 0.066) and disposition index (DI) (Bonferroni P = 0.072). We conclude that rs11705701 in IGF2BP2 is associated with body fat and this effect on body fat influences insulin resistance which may contribute to T2DM risk.
登录
查看更多内容
影响因子：
5.4
作者：
Boston, Ray C;Stefanovski, Darko;Bergman, Richard N
通讯作者：
Bergman, Richard N
影响因子：
168.9
作者：
Peters, RK;Kjos, SL;Buchanan, TA
通讯作者：
Buchanan, TA
影响因子：
2.1
作者：
Blangero, J;Williams, JT;Almasy, L
通讯作者：
Almasy, L
影响因子：
7.7
作者：
Palmer, Nicholette D.;Goodarzi, Mark O.;Bowden, Donald W.
通讯作者：
Bowden, Donald W.
影响因子：
9.8
作者：
O'Connell, JR;Weeks, DE
通讯作者：
Weeks, DE