Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI.
Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI.
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DOI：
10.2337/db07-1466
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发表时间：
2008-05
期刊：
影响因子：
7.7
通讯作者：
Frayling TM
中科院分区：
文献类型：
--
作者：
Freathy RM;Timpson NJ;Lawlor DA;Pouta A;Ben-Shlomo Y;Ruokonen A;Ebrahim S;Shields B;Zeggini E;Weedon MN;Lindgren CM;Lango H;Melzer D;Ferrucci L;Paolisso G;Neville MJ;Karpe F;Palmer CN;Morris AD;Elliott P;Jarvelin MR;Smith GD;McCarthy MI;Hattersley AT;Frayling TM
FTO基因的常见变异与BMI和2型糖尿病有关。BMI增加与糖尿病风险因素相关，包括胰岛素、葡萄糖和甘油三酯升高。我们的目的是测试FTO基因型是否与这些代谢性状的变异相关。我们使用来自17,037名欧洲白色个体的数据，检验了FTO基因型与10种代谢性状之间的关联。我们将观察到的FTO基因型对每个性状的影响与FTO-BMI和BMI-性状相关性的预期影响进行了比较。FTO rs 9939609 A等位基因的每个拷贝与较高的空腹胰岛素水平相关。（0.039 SD [95% CI 0.013-0.064]; P = 0.003），葡萄糖（0.024 [0.001- 0.048]; P = 0.044），甘油三酯（0.028 [0.003- 0.052]; P = 0.025）和低HDL胆固醇（0.032 [0.008 - 0.057]; P = 0.009）。当调整BMI时，没有证据表明这些关联。与空腹丙氨酸氨基转移酶、γ-谷氨酰转移酶、LDL胆固醇、A1 C、收缩压和舒张压的相关性在预期方向，但未达到P < 0.05。对于所有代谢性状，效应量与BMI中每个等位基因变化的预期值一致。FTO基因型与代谢综合征的几率较高相关（比值比1.17 [95%CI 1.10 - 1.25]; P = 3 × 10−6）。FTO基因型与代谢特征相关，其程度与其对BMI的影响完全一致。需要> 12，000个个体的样本量来检测P < 0.05的关联。我们的研究结果强调了使用适当的动力研究来评估已知糖尿病或肥胖变异对与这些疾病相关的次要特征的影响的重要性。
Common variation in the FTO gene is associated with BMI and type 2 diabetes. Increased BMI is associated with diabetes risk factors, including raised insulin, glucose, and triglycerides. We aimed to test whether FTO genotype is associated with variation in these metabolic traits. We tested the association between FTO genotype and 10 metabolic traits using data from 17,037 white European individuals. We compared the observed effect of FTO genotype on each trait to that expected given the FTO-BMI and BMI-trait associations. Each copy of the FTO rs9939609 A allele was associated with higher fasting insulin (0.039 SD [95% CI 0.013–0.064]; P = 0.003), glucose (0.024 [0.001– 0.048]; P = 0.044), and triglycerides (0.028 [0.003– 0.052]; P = 0.025) and lower HDL cholesterol (0.032 [0.008 – 0.057]; P = 0.009). There was no evidence of these associations when adjusting for BMI. Associations with fasting alanine aminotransferase, γ-glutamyl-transferase, LDL cholesterol, A1C, and systolic and diastolic blood pressure were in the expected direction but did not reach P < 0.05. For all metabolic traits, effect sizes were consistent with those expected for the per allele change in BMI. FTO genotype was associated with a higher odds of metabolic syndrome (odds ratio 1.17 [95% CI 1.10 –1.25]; P = 3 × 10−6). FTO genotype is associated with metabolic traits to an extent entirely consistent with its effect on BMI. Sample sizes of >12,000 individuals were needed to detect associations at P < 0.05. Our findings highlight the importance of using appropriately powered studies to assess the effects of a known diabetes or obesity variant on secondary traits correlated with these conditions.
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DOI：
10.1111/j.1532-5415.2000.tb03873.x
发表时间：
2000-12-01
影响因子：
6.3
作者：
Ferrucci, L;Bandinelli, S;Guralnik, JM
通讯作者：
Guralnik, JM
影响因子：
2.8
作者：
Knight, B;Shields, BM;Hattersley, AT
通讯作者：
Hattersley, AT
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.
影响因子：
3.5
作者：
Ohashi, Jun;Naka, Izumi;Ohtsuka, Ryutaro
通讯作者：
Ohtsuka, Ryutaro
影响因子：
7.7
作者：
Sattar, Naveed;McConnachie, Alex;Packard, Chris
通讯作者：
Packard, Chris