Polymorphisms in the NPY2R gene show significant associations with BMI that are additive to FTO, MC4R, and NPFFR2 gene effects.
Polymorphisms in the NPY2R gene show significant associations with BMI that are additive to FTO, MC4R, and NPFFR2 gene effects.
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DOI：
10.1038/oby.2011.239
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发表时间：
2011-11
期刊：
影响因子：
6.9
通讯作者：
Adams, Ted D.
中科院分区：
文献类型：
--
作者：
Hunt, Steven C.;Hasstedt, Sandra J.;Xin, Yuanpei;Dalley, Brian K.;Milash, Brett A.;Yakobson, Emanuel;Gress, Richard E.;Davidson, Lance E.;Adams, Ted D.
神经肽 Y (NPY) 是一种食欲激素，主要控制进食行为。 NPY2R 是 5 个 NPY 受体基因之一，其 5' 和外显子 2 区域与肥胖的关系微弱且不一致。由于该基因的 ATG 起始位点位于外显子 2 的开头，跨内含子 1 的 SNP 可能显示出比预期更强的与肥胖的关联。对 2985 名犹他州白人受试者进行了 2 个 5' SNP、3 个内含子 1 SNP 和 1 个同义外显子 2 SNP 的基因分型。之前相关的 FTO、NPY、NPY1R、MC4R、PPARGC1A、OR7D4 和四个 NPFFR2 SNP 也进行了基因分型并与 BMI 相关。一个 NPY2R 5' SNP（rs12649641，p=0.008）、一个外显子 2 SNP（rs2880415，p=0.009）和一个内含子 1 SNP（rs17376826，p=7×10−6）均与 BMI 显着相关。所有 3 个 SNP，加上 FTO（rs9939609，p=1.5×10−6）和两个 NPFFR2 SNP（rs4129733，p=3.7×10−13 和 rs11940196，4.2×10−10）在多元回归加性模型中仍然显着。使用 NPY2R、NPFFR2 和 MC4R 估计单倍型的双倍型与 BMI 显着相关（分别为 p=1.0×10−10、3.2×10−8 和 1.1×10−4）。 NPY2R、NPFFR2 和 MC4R 的单倍型，加上 FTO SNP，解释了 9.6% 的 BMI 方差。四个基因的每个等位基因的 SNP 效应大小范围为 0.8 至 3.5 kg/m2。我们得出的结论是，NPY2R 内含子 1 中含有 rs17376826 SNP 的单倍型与 BMI 具有很强的相关性，一些 NPFFR2 单倍型对肥胖有很强的保护作用或增加肥胖的风险，并且 NPY2R 和 NPFFR2 在独立于 FTO 和 MC4R 的肥胖倾向中发挥着重要作用。
Neuropeptide Y (NPY) is an appetite hormone that acts centrally to control feeding behavior. The 5’ and exon 2 regions of NPY2R, one of 5 NPY receptor genes, have been weakly and inconsistently implicated with obesity. With the ATG start site of the gene at the beginning of exon 2, SNPs across intron 1 may show stronger associations with obesity than expected. Two 5’ SNPs, three intron 1 SNPs, and one synonymous exon 2 SNP were genotyped on 2985 Caucasian Utah subjects. Previously associated FTO, NPY, NPY1R, MC4R, PPARGC1A, OR7D4, and four NPFFR2 SNPs were also genotyped and related to BMI. One NPY2R 5’ SNP (rs12649641, p=0.008), an exon 2 SNP (rs2880415, p=0.009), and an intron 1 SNP (rs17376826, p=7×10−6) were each significantly associated with BMI. All 3 SNPs, plus FTO (rs9939609, p=1.5×10−6) and two NPFFR2 SNPs (rs4129733, p=3.7×10−13 and rs11940196, 4.2×10−10) remained significant in a multiple regression additive model. Diplotypes using the estimated haplotypes of NPY2R, NPFFR2, and MC4R were significantly associated with BMI (p=1.0×10−10, 3.2×10−8, and 1.1×10−4, respectively). Haplotypes of NPY2R, NPFFR2, and MC4R, plus the FTO SNP, explained 9.6% of the BMI variance. SNP effect sizes per allele for the four genes ranged from 0.8 to 3.5 kg/m2. We conclude that haplotypes containing the rs17376826 SNP in intron 1 of NPY2R have strong associations with BMI, some NPFFR2 haplotypes are strongly protective against or increase risk of obesity, and both NPY2R and NPFFR2 play important roles in obesity predisposition independent of FTO and MC4R.
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影响因子：
30.8
作者：
通讯作者：
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DOI：
10.1111/j.1749-6632.2003.tb03161.x
发表时间：
2003-01-01
期刊：
MELANOCORTIN SYSTEM
影响因子：
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作者：
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通讯作者：
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作者：
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影响因子：
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作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
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影响因子：
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作者：
Loos, Ruth J. F.;Lindgren, Cecilia M.;Li, Shengxu;Wheeler, Eleanor;Zhao, Jing Hua;Prokopenko, Inga;Inouye, Michael;Freathy, Rachel M.;Attwood, Antony P.;Beckmann, Jacques S.;Berndt, Sonja I.;Bergmann, Sven;Bennett, Amanda J.;Bingham, Sheila A.;Bochud, Murielle;Brown, Morris;Cauchi, Stephane;Connell, John M.;Cooper, Cyrus;Smith, George Davey;Day, Ian;Dina, Christian;De, Subhajyoti;Dermitzakis, Emmanouil T.;Doney, Alex S. F.;Elliott, Katherine S.;Elliott, Paul;Evans, David M.;Farooqi, I. Sadaf;Froguel, Philippe;Ghori, Jilur;Groves, Christopher J.;Gwilliam, Rhian;Hadley, David;Hall, Alistair S.;Hattersley, Andrew T.;Hebebrand, Johannes;Heid, Iris M.;Herrera, Blanca;Hinney, Anke;Hunt, Sarah E.;Jarvelin, Marjo-Riitta;Johnson, Toby;Jolley, Jennifer D. M.;Karpe, Fredrik;Keniry, Andrew;Khaw, Kay-Tee;Luben, Robert N.;Mangino, Massimo;Marchini, Jonathan;McArdle, Wendy L.;McGinnis, Ralph;Meyre, David;Munroe, Patricia B.;Morris, Andrew D.;Ness, Andrew R.;Neville, Matthew J.;Nica, Alexandra C.;Ong, Ken K.;O'Rahilly, Stephen;Owen, Katharine R.;Palmer, Colin N. A.;Papadakis, Konstantinos;Potter, Simon;Pouta, Anneli;Qi, Lu;Randall, Joshua C.;Rayner, Nigel W.;Ring, Susan M.;Sandhu, Manjinder S.;Scherag, Andre;Sims, Matthew A.;Song, Kijoung;Soranzo, Nicole;Speliotes, Elizabeth K.;Syddall, Holly E.;Teichmann, Sarah A.;Timpson, Nicholas J.;Tobias, Jonathan H.;Uda, Manuela;Vogel, Carla I. Ganz;Wallace, Chris;Waterworth, Dawn M.;Weedon, Michael N.;Willer, Cristen J.;Wraight, Vicki L.;Yuan, Xin;Zeggini, Eleftheria;Hirschhorn, Joel N.;Strachan, David P.;Ouwehand, Willem H.;Caulfield, Mark J.;Samani, Nilesh J.;Frayling, Timothy M.;Vollenweider, Peter;Waeber, Gerard;Mooser, Vincent;Deloukas, Panos;McCarthy, Mark I.;Wareham, Nicholas J.;Barroso, Ines
通讯作者：
Barroso, Ines