PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease.
PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease.
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DOI：
10.1002/hep.23768
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发表时间：
2010-09
期刊：
影响因子：
13.5
通讯作者：
Hirschhorn, Joel N.
中科院分区：
文献类型：
--
作者：
Speliotes, Elizabeth K.;Butler, Johannah L.;Palmer, Cameron D.;Voight, Benjamin F.;Hirschhorn, Joel N.
7个位点附近的单核苷酸多态性（SNPs）与肝功能检查或磁共振波谱与肝脏脂肪变性相关。在这项研究中，我们的目的是测试这些SNPs是否影响组织学证实的非酒精性脂肪性肝病（NAFLD）的风险。我们检测了来自非酒精性脂肪性肝炎临床研究网络的592例欧洲血统病例和1405例血统匹配的对照组的组织学NAFLD与7个位点的SNPs的相关性。PNPLA 3中rs738409的G等位基因与组织学NAFLD的几率增加相关（比值比[OR] = 3.26，95%置信区间[CI] = 2.11-7.21; P = 3.6 × 10−43）。在一例病例中，仅PNPLA 3中rs738409的G等位基因分析与3区中心脂肪变性风险降低相关（OR = 0.46，95%CI = 0.36-0.58; P = 5.15 × 10−11）。我们没有观察到这种变异与体重指数、甘油三酯水平、高密度脂蛋白和低密度脂蛋白水平或糖尿病有任何关联（P > 0.05）。其他6个位点的变异均与NAFLD无关。PNPLA 3的遗传变异使NAFLD的组织学特征日益严重的风险显著增加，而对代谢综合征组分特征没有强烈的影响。
Single nucleotide polymorphisms (SNPs) near 7 loci have been associated with liver function tests or with liver steatosis by magnetic resonance spectroscopy. In this study we aim to test whether these SNPs influence the risk of histologically-confirmed nonalcoholic fatty liver disease (NAFLD). We tested the association of histologic NAFLD with SNPs at 7 loci in 592 cases of European ancestry from the Nonalcoholic Steatohepatitis Clinical Research Network and 1405 ancestry-matched controls. The G allele of rs738409 in PNPLA3 was associated with increased odds of histologic NAFLD (odds ratio [OR] = 3.26, 95% confidence intervals [CI] = 2.11-7.21; P = 3.6 × 10−43). In a case only analysis of G allele of rs738409 in PNPLA3 was associated with a decreased risk of zone 3 centered steatosis (OR = 0.46, 95% CI = 0.36-0.58; P = 5.15 × 10−11). We did not observe any association of this variant with body mass index, triglyceride levels, high- and low-density lipoprotein levels, or diabetes (P > 0.05). None of the variants at the other 6 loci were associated with NAFLD. Genetic variation at PNPLA3 confers a markedly increased risk of increasingly severe histological features of NAFLD, without a strong effect on metabolic syndrome component traits.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
30.8
作者：
Zeggini, Eleftheria;Scott, Laura J.;Saxena, Richa;Voight, Benjamin F.;Marchini, Jonathan L.;Hu, Tianle;de Bakker, Paul I. W.;Abecasis, Goncalo R.;Almgren, Peter;Andersen, Gitte;Ardlie, Kristin;Bostroem, Kristina Bengtsson;Bergman, Richard N.;Bonnycastle, Lori L.;Borch-Johnsen, Knut;Burtt, Noel P.;Chen, Hong;Chines, Peter S.;Daly, Mark J.;Deodhar, Parimal;Ding, Chia-Jen;Doney, Alex S. F.;Duren, William L.;Elliott, Katherine S.;Erdos, Michael R.;Frayling, Timothy M.;Freathy, Rachel M.;Gianniny, Lauren;Grallert, Harald;Grarup, Niels;Groves, Christopher J.;Guiducci, Candace;Hansen, Torben;Herder, Christian;Hitman, Graham A.;Hughes, Thomas E.;Isomaa, Bo;Jackson, Anne U.;Jorgensen, Torben;Kong, Augustine;Kubalanza, Kari;Kuruvilla, Finny G.;Kuusisto, Johanna;Langenberg, Claudia;Lango, Hana;Lauritzen, Torsten;Li, Yun;Lindgren, Cecilia M.;Lyssenko, Valeriya;Marvelle, Amanda F.;Meisinger, Christa;Midthjell, Kristian;Mohlke, Karen L.;Morken, Mario A.;Morris, Andrew D.;Narisu, Narisu;Nilsson, Peter;Owen, Katharine R.;Palmer, Colin N. A.;Payne, Felicity;Perry, John R. B.;Pettersen, Elin;Platou, Carl;Prokopenko, Inga;Qi, Lu;Qin, Li;Rayner, Nigel W.;Rees, Matthew;Roix, Jeffrey J.;Sandbaek, Anelli;Shields, Beverley;Sjogren, Marketa;Steinthorsdottir, Valgerdur;Stringham, Heather M.;Swift, Amy J.;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Timpson, Nicholas J.;Tuomi, Tiinamaija;Tuomilehto, Jaakko;Walker, Mark;Watanabe, Richard M.;Weedon, Michael N.;Willer, Cristen J.;Illig, Thomas;Hveem, Kristian;Hu, Frank B.;Laakso, Markku;Stefansson, Kari;Pedersen, Oluf;Wareham, Nicholas J.;Barroso, Ines;Hattersley, Andrew T.;Collins, Francis S.;Groop, Leif;McCarthy, Mark I.;Boehnke, Michael;Altshuler, David
通讯作者：
Altshuler, David
DOI：
10.1111/j.1440-1746.2005.04058.x
发表时间：
2005-12-01
影响因子：
4.1
作者：
Fan, JG;Zhu, JN;Chen, SY
通讯作者：
Chen, SY
影响因子：
25.7
作者：
Fan, JG;Zhu, J;Chen, SY
通讯作者：
Chen, SY
影响因子：
5.1
作者：
Harrison, Stephen A;Neuschwander-Tetri, Brent A
通讯作者：
Neuschwander-Tetri, Brent A