Glucuronic acid epimerase is associated with plasma triglyceride and high-density lipoprotein cholesterol levels in Turks.
Glucuronic acid epimerase is associated with plasma triglyceride and high-density lipoprotein cholesterol levels in Turks.
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DOI：
10.1111/j.1469-1809.2011.00644.x
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发表时间：
2011-05
影响因子：
1.9
通讯作者：
Mahley RW
中科院分区：
文献类型：
--
作者：
Hodoğlugil U;Williamson DW;Yu Y;Farrer LA;Mahley RW
我们通过精细定位缩小了染色体15q21-23与血浆高密度脂蛋白胆固醇(HDLC)水平的连锁范围，然后重点研究了葡萄糖醛酸差向异构酶(GLCE)，一种硫酸乙酰肝素蛋白多糖(HSPG)的生物合成酶。HSPG与载脂蛋白E一起参与脂代谢。在GLCE基因座的31个SNP中，有9个单倍型分析与血浆高密度脂蛋白胆固醇和甘油三酯水平相关(置换后的p分别为0.006和0.013)。在两组无关受试者中的五个标记GLCE SNP中，有三个(rs16952868、rs11631403、rs3865014)与男性的甘油三酯和高密度脂蛋白胆固醇水平有关(非置换p<；0.05)。这种关联在APOE 2/3受试者中更强(APOE2减少了与HSPGs的结合)，并在男性和女性(n=2612)中达到多重测试意义(p<；0.05)。在第二个队列(n=1164)中也得到了类似的结果。有趣的是，在GLCE基因座上，以重组热点为界，土耳其人的SNPs的等位基因频率很少，与中国人相似，而不是欧洲人；15号染色体上的相邻区域类似于欧洲人的模式。对喂食食物或高脂饮食的GLCE+/-APOE-/-小鼠的研究支持GLCE在脂类代谢中的作用。因此，GLCE中的SNPs与土耳其人的甘油三酯和高密度脂蛋白-C水平有关，小鼠研究也支持GLCE在脂质代谢中的作用。
We narrowed chromosome 15q21-23 linkage to plasma high density lipoprotein cholesterol (HDL-C) levels in atherogenic dyslipidemic Turkish families by fine mapping, then focused on glucuronic acid epimerase (GLCE), a heparan sulfate proteoglycan (HSPG) biosynthesis enzyme. HSPGs participate in lipid metabolism along with apolipoprotein (apo) E. Of 31 SNPs in the GLCE locus, nine analyzed by haplotype were associated with plasma HDL-C and triglyceride levels (permuted p = 0.006 and 0.013, respectively) in families. Of five tagging GLCE SNPs in two cohorts of unrelated subjects, three (rs16952868, rs11631403, rs3865014) were associated with triglyceride and HDL-C levels in males (non-permuted p < 0.05). The association was stronger in APOE 2/3 subjects (apoE2 has reduced binding to HSPGs) and reached multiple-testing significance (p < 0.05) in both males and females (n = 2612). Similar results were obtained in the second cohort (n = 1164). Interestingly, at the GLCE locus, bounded by recombination hotspots, Turks had a minor allele frequency of SNPs resembling Chinese more than European ancestry; adjoining regions on chromosome 15 resembled the European pattern. Studies of glce+/–apoe–/– mice fed a chow or high-fat diet supported a role for GLCE in lipid metabolism. Thus, SNPs in GLCE are associated with triglyceride and HDL-C levels in Turks, and mouse studies support a role for glce in lipid metabolism.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
14.9
作者：
Blake JA;Bult CJ;Eppig JT;Kadin JA;Richardson JE;Mouse Genome Database Group
通讯作者：
Mouse Genome Database Group
DOI：
10.1073/pnas.0700724104
发表时间：
2007-11-06
影响因子：
11.1
作者：
Guo, Yinglying;Lu, Peng;Peltz, Gary
通讯作者：
Peltz, Gary
影响因子：
5.3
作者：
Hodoglugil, U;Williamson, DW;Mahley, RW
通讯作者：
Mahley, RW
影响因子：
5.3
作者：
Feitosa, Mary F.;Province, Michael A.;Borecki, Ingrid B.
通讯作者：
Borecki, Ingrid B.