A Rare Variant in the Visfatin Gene (NAMPT/PBEF1) Is Associated With Protection From Obesity
A Rare Variant in the Visfatin Gene (NAMPT/PBEF1) Is Associated With Protection From Obesity
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DOI：
10.1038/oby.2009.75
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发表时间：
2009-08-01
期刊：
影响因子：
6.9
通讯作者：
Walley, Andrew J.
中科院分区：
文献类型：
--
作者：
Blakemore, Alexandra I. F.;Meyre, David;Walley, Andrew J.
Visfatin是最近报道的一种由NAMPT(PBEF1)基因编码的新型脂肪因子。本研究旨在研究Visfatin基因的单核苷酸多态(SNPs)与肥胖或2型糖尿病(T2D)相关的可能性。选择了一组8个“Tag-SNPs”，并设计了ABI SNPlex基因分型方法。共有1709名严重肥胖受试者(896名III级肥胖成年人和813名儿童)以及2367名T2D个体和2850名对照组被分型。为了进行数量性状分析，另有2362名受试者从普通人群样本中进行了rs10487818的分型。位于NAMPT基因第4内含子的一个罕见的SNP rs10487818与重度肥胖有关，其等位基因频率在对照组为1.6%，在III类肥胖组为0.4%，在重度肥胖组为0。在儿童(P=6×10(-9))和成人(P=8×10(-5))中，观察到罕见等位基因(A，A)与(A，T+T，T)基因型的存在或不存在存在高度显著的相关性。没有观察到这种或任何其他SNP与肥胖或T2D之间的其他显著关联(P<；0.05)。在一般人群样本(n=5,212)中，未观察到与BMI或腰臀比相关。这是首批被证明对常见多基因疾病具有保护作用的罕见SNPs之一，并提供了进一步的证据，表明具有强效应的稀有等位基因可能导致严重肥胖等复杂疾病。
Visfatin was recently reported as a novel adipokine encoded by the NAMPT (PBEF1) gene. This study was aimed at investigation of the possibility that single-nucleotide polymorphisms (SNPs) in the visfatin gene are associated with either obesity or type 2 diabetes (T2D). A set of eight "tag-SNPs" were selected and ABI SNPlex assays designed for genotyping purposes. A total of 1,709 severely obese subjects were typed (896 class III obese adults and 813 children) together with 2,367 T2D individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. One rare SNP, rs10487818, located in intron 4 of NAMPT was associated with severe obesity, with a minor allele frequency of 1.6% in controls, 0.4% in the class III obese adults and, remarkably, 0% in the severely obese children. A highly significant association was observed for the presence or absence of the rare allele, i.e., (A, A) vs. (A, T + T, T) genotypes, in children (P = 6 x 10(-9)) and in adults (P = 8 x 10(-5)). No other significant (P < 0.05) association was observed with obesity or T2D for this or any other SNP. No association with BMI or waist-to-hip ratio was observed in a general population sample (n = 5,212). This is one of the first rare SNPs shown to be protective against a common polygenic disease and provides further evidence that rare alleles of strong effect can contribute to complex diseases such as severe obesity.