Variants in CPA1 are strongly associated with early onset chronic pancreatitis.
Variants in CPA1 are strongly associated with early onset chronic pancreatitis.
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DOI：
10.1038/ng.2730
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发表时间：
2013-10
期刊：
影响因子：
30.8
通讯作者：
Sahin-Toth, Miklos
中科院分区：
文献类型：
--
作者：
Witt, Heiko;Beer, Sebastian;Rosendahl, Jonas;Chen, Jian-Min;Chandak, Giriraj Ratan;Masamune, Atsushi;Bence, Melinda;Szmola, Richard;Oracz, Grzegorz;Macek, Milan, Jr.;Bhatia, Eesh;Steigenberger, Sandra;Lasher, Denise;Buehler, Florence;Delaporte, Catherine;Tebbing, Johanna;Ludwig, Maren;Pilsak, Claudia;Saum, Karolin;Bugert, Peter;Masson, Emmanuelle;Paliwal, Sumit;Bhaskar, Seema;Sobczynska-Tomaszewska, Agnieszka;Bak, Daniel;Balascak, Ivan;Choudhuri, Gourdas;Reddy, D. Nageshwar;Rao, G. Venkat;Thomas, Varghese;Kume, Kiyoshi;Nakano, Eriko;Kakuta, Yoichi;Shimosegawa, Tooru;Durko, Lukasz;Szabo, Andras;Schnur, Andrea;Hegyi, Peter;Rakonczay, Zoltan, Jr.;Pfuetzer, Roland;Schneider, Alexander;Groneberg, David Alexander;Braun, Markus;Schmidt, Hartmut;Witt, Ulrike;Friess, Helmut;Alguel, Hana;Landt, Olfert;Schuelke, Markus;Krueger, Renate;Wiedenmann, Bertram;Schmidt, Frank;Zimmer, Klaus-Peter;Kovacs, Peter;Stumvoll, Michael;Blueher, Matthias;Mueller, Thomas;Janecke, Andreas;Teich, Niels;Gruetzmann, Robert;Schulz, Hans-Ulrich;Moessner, Joachim;Keim, Volker;Loehr, Matthias;Ferec, Claude;Sahin-Toth, Miklos
慢性胰腺炎是一种胰腺炎症性疾病。我们在一个德国发现队列和三个复制队列中分析了非酒精性慢性胰腺炎受试者和对照组中CPA1编码的羧基肽酶A1。在29/944(3.1%)德国患者和5/3,938(0.1%)对照组中存在功能受损的变异(优势比[OR]=24.9；P=1.5×10-16)。这种关联在≤10岁的受试者中最强(9.7%；OR=84.0；P=4.1×10-24)。在复制队列中，8/6 0 0(1.3%)患者和9/2 4 32(0.4%)来自欧洲的对照(P=0.0 1)，5/2 30(2.2%)患者和0/2 64对照(P=0.0 2)，5/2 47(2.0%)患者(2.0%)和0/34 1(日本对照)(P=0.013)。CPA1变异增加胰腺炎风险的机制可能涉及错误折叠诱导的内质网应激，而不是像其他遗传风险因素所看到的胰酶活性升高。
Chronic pancreatitis is an inflammatory disorder of the pancreas. We analyzed CPA1 encoding carboxypeptidase A1 in subjects with non-alcoholic chronic pancreatitis and controls in a German discovery cohort and three replication cohorts. Functionally impaired variants were present in 29/944 (3.1%) German patients and in 5/3,938 (0.1%) controls (odds ratio [OR] = 24.9; P = 1.5 × 10-16). The association was strongest in subjects aged ≤10 years (9.7%; OR = 84.0; P = 4.1 × 10-24). In the replication cohorts, defective CPA1 variants were observed in 8/600 (1.3%) patients and in 9/2,432 (0.4%) controls from Europe (P = 0.01), in 5/230 (2.2%) patients and 0/264 controls from India (P = 0.02), and in 5/247 (2.0%) patients but 0/341 controls from Japan (P = 0.013). The mechanism of increased pancreatitis risk by CPA1 variants may involve misfolding-induced endoplasmic reticulum stress rather than elevated trypsin activity as seen with other genetic risk factors.
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影响因子：
30.8
作者：
Rosendahl, Jonas;Witt, Heiko;Sahin-Toth, Miklos
通讯作者：
Sahin-Toth, Miklos
影响因子：
30.8
作者：
Whitcomb, David C.;LaRusch, Jessica;Krasinskas, Alyssa M.;Klei, Lambertus;Smith, Jill P.;Brand, Randall E.;Neoptolemos, John P.;Lerch, Markus M.;Tector, Matt;Sandhu, Bimaljit S.;Guda, Nalini M.;Orlichenko, Lidiya;Alkaade, Samer;Amann, Stephen T.;Anderson, Michelle A.;Baillie, John;Banks, Peter A.;Conwell, Darwin;Cote, Gregory A.;Cotton, Peter B.;DiSario, James;Farrer, Lindsay A.;Forsmark, Chris E.;Johnstone, Marianne;Gardner, Timothy B.;Gelrud, Andres;Greenhalf, William;Haines, Jonathan L.;Hartman, Douglas J.;Hawes, Robert A.;Lawrence, Christopher;Lewis, Michele;Mayerle, Julia;Mayeux, Richard;Melhem, Nadine M.;Money, Mary E.;Muniraj, Thiruvengadam;Papachristou, Georgios I.;Pericak-Vance, Margaret A.;Romagnuolo, Joseph;Schellenberg, Gerard D.;Sherman, Stuart;Simon, Peter;Singh, Vijay P.;Slivka, Adam;Stolz, Donna;Sutton, Robert;Weiss, Frank Ulrich;Wilcox, C. Mel;Zarnescu, Narcis Octavian;Wisniewski, Stephen R.;O'Connell, Michael R.;Kienholz, Michelle L.;Roeder, Kathryn;Barmada, M. Michael;Yadav, Dhiraj;Devlin, Bernie;Albert, Marilyn S.;Albin, Roger L.;Apostolova, Liana G.;Arnold, Steven E.;Baldwin, Clinton T.;Barber, Robert;Barnes, Lisa L.;Beach, Thomas G.;Beecham, Gary W.;Beekly, Duane;Bennett, David A.;Bigio, Eileen H.;Bird, Thomas D.;Blacker, Deborah;Boxer, Adam;Burke, James R.;Buxbaum, Joseph D.;Cairns, Nigel J.;Cantwell, Laura B.;Cao, Chuanhai;Carney, Regina M.;Carroll, Steven L.;Chui, Helena C.;Clark, David G.;Cribbs, David H.;Crocco, Elizabeth A.;Cruchaga, Carlos;DeCarli, Charles;Demirci, F. Yesim;Dick, Malcolm;Dickson, Dennis W.;Duara, Ranjan;Ertekin-Taner, Nilufer;Faber, Kelley M.;Fallon, Kenneth B.;Farlow, Martin R.;Ferris, Steven;Foroud, Tatiana M.;Frosch, Matthew P.;Galasko, Douglas R.;Ganguli, Mary;Gearing, Marla;Geschwind, Daniel H.;Ghetti, Bernardino;Gilbert, John R.;Gilman, Sid;Glass, Jonathan D.;Goate, Alison M.;Graff-Radford, Neill R.;Green, Robert C.;Growdon, John H.;Hakonarson, Hakon;Hamilton-Nelson, Kara L.;Hamilton, Ronald L.;Harrell, Lindy E.;Head, Elizabeth;Honig, Lawrence S.;Hulette, Christine M.;Hyman, Bradley T.;Jicha, Gregory A.;Jin, Lee-Way;Jun, Gyungah;Kamboh, M. Ilyas;Karydas, Anna;Kaye, Jeffrey A.;Kim, Ronald;Koo, Edward H.;Kowall, Neil W.;Kramer, Joel H.;Kramer, Patricia;Kukull, Walter A.;LaFerla, Frank M.;Lah, James J.;Leverenz, James B.;Levey, Allan I.;Li, Ge;Lin, Chiao-Feng;Lieberman, Andrew P.;Lopez, Oscar L.;Lunetta, Kathryn L.;Lyketsos, Constantine G.;Mack, Wendy J.;Marson, Daniel C.;Martin, Eden R.;Martiniuk, Frank;Mash, Deborah C.;Masliah, Eliezer;McKee, Ann C.;Mesulam, Marsel;Miller, Bruce L.;Miller, Carol A.;Miller, Joshua W.;Montine, Thomas J.;Morris, John C.;Murrell, Jill R.;Naj, Adam C.;Olichney, John M.;Parisi, Joseph E.;Peskind, Elaine;Petersen, Ronald C.;Pierce, Aimee;Poon, Wayne W.;Potter, Huntington;Quinn, Joseph F.;Raj, Ashok;Raskind, Murray;Reiman, Eric M.;Reisberg, Barry;Reitz, Christiane;Ringman, John M.;Roberson, Erik D.;Rosen, Howard J.;Rosenberg, Roger N.;Sano, Mary;Saykin, Andrew J.;Schneider, Julie A.;Schneider, Lon S.;Seeley, William W.;Smith, Amanda G.;Sonnen, Joshua A.;Spina, Salvatore;Stern, Robert A.;Tanzi, Rudolph E.;Trojanowski, John Q.;Troncoso, Juan C.;Tsuang, Debby W.;Valladares, Otto;Van Deerlin, Vivianna M.;Van Eldik, Linda J.;Vardarajan, Badri N.;Vinters, Harry V.;Vonsattel, Jean Paul;Wang, Li-San;Weintraub, Sandra;Welsh-Bohmer, Kathleen A.;Williamson, Jennifer;Woltjer, Randall L.;Wright, Clinton B.;Younkin, Steven G.;Yu, Chang-En;Yu, Lei
通讯作者：
Yu, Lei
影响因子：
2.9
作者：
Mock, WL;Liu, YY;Stanford, DJ
通讯作者：
Stanford, DJ
影响因子：
30.8
作者：
Le Marechal, Cedric;Masson, Emmanuelle;Ferec, Claude
通讯作者：
Ferec, Claude
影响因子：
24.5
作者：
Beer S;Zhou J;Szabó A;Keiles S;Chandak GR;Witt H;Sahin-Tóth M
通讯作者：
Sahin-Tóth M