The Fat Mass and Obesity Associated Gene, FTO, Is Also Associated with Osteoporosis Phenotypes
The Fat Mass and Obesity Associated Gene, FTO, Is Also Associated with Osteoporosis Phenotypes
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脂肪量和肥胖相关基因 FTO 也与骨质疏松症表型相关
DOI：
10.1371/journal.pone.0027312
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发表时间：
2011-11-18
期刊：
影响因子：
3.7
通讯作者：
Deng, Hong-Wen
中科院分区：
文献类型：
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作者：
Guo, Yan;Liu, Hui;Deng, Hong-Wen
肥胖和骨质疏松症在遗传上密切相关。FTO基因一直被认为与肥胖表型相关。最近的一项研究报告说，缺乏Fto的小鼠可能导致骨矿物质密度（BMD）降低。因此，我们推测FTO基因可能对骨质疏松症表型也很重要。为了验证这一假设，我们进行了关联分析，以调查FTO中的SNP与髋部和脊柱BMD之间的关系。在两个独立的中国人群（分别为818和809名无关的汉族受试者）和一个高加索人群（2，286名无关的受试者）中共检测了141个SNP。结合这两个中国样本，我们确定了FTO中的6个SNPs在多次检验调整后与髋部BMD显著相关，合并P值范围为4.99×10−4-1.47×10−4。这6个SNPs均位于FTO基因的第8内含子上，且处于高度连锁不平衡状态。每个SNP的每个次要等位基因拷贝与髋部BMD值增加相关，在中国样本1和2中的效应量（β）分别为0.025和0.015。然而，这6个SNP中没有一个在高加索人样本中显示出显著的关联信号，表现出一定程度的种族差异。我们的研究结果，结合先前的生物学证据，提示FTO基因可能是中国人群BMD变异和骨质疏松症的一个新的候选基因。
Obesity and osteoporosis are closely correlated genetically. FTO gene has been consistently identified to be associated with obesity phenotypes. A recent study reported that the mice lacking Fto could result in lower bone mineral density (BMD). Thus, we hypothesize that the FTO gene might be also important for osteoporosis phenotypes. To test for such a hypothesis, we performed an association analyses to investigate the relationship between SNPs in FTO and BMD at both hip and spine. A total of 141 SNPs were tested in two independent Chinese populations (818 and 809 unrelated Han subjects, respectively) and a Caucasian population (2,286 unrelated subjects). Combining the two Chinese samples, we identified 6 SNPs in FTO to be significantly associated with hip BMD after multiple testing adjustments, with the combined P values ranged from 4.99×10−4–1.47×10−4. These 6 SNPs are all located at the intron 8 of FTO and in high linkage disequilibrium. Each copy of the minor allele of each SNP was associated with increased hip BMD values with the effect size (beta) of ∼0.025 and ∼0.015 in the Chinese sample 1 and 2, respectively. However, none of these 6 SNPs showed significant association signal in the Caucasian sample, by presenting some extent of ethnic difference. Our findings, together with the prior biological evidence, suggest that the FTO gene might be a new candidate for BMD variation and osteoporosis in Chinese populations.