التفاصيل البيبلوغرافية
العنوان:
Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis
المؤلفون:
Marla Gearing , David G. Clark , Steven L. Carroll , Marianne Johnstone , Darwin L. Conwell , Gregory A. Cote , Sandra Weintraub , Matthew P. Frosch , Stuart Sherman , Badri N. Vardarajan , Joshua A. Sonnen , Lindy E. Harrell , Peter B. Cotton , Lisa L. Barnes , Lawrence S. Honig , Carol A. Miller , Adam Slivka , Michelle A. Anderson , Nadine M. Melhem , David A. Bennett , Joel H. Kramer , Jill P. Smith , Michele D. Lewis , Mary Ganguli , Jean Paul Vonsatte , Thomas J. Montine , Lee-Way Jin , Kenneth B. Fallon , Marilyn S. Albert , Eliezer Masliah , John H. Growdon , Barry Reisberg , Chuanhai Cao , Patricia L. Kramer , Douglas J. Hartman , Allan I. Levey , Jennifer Williamson , Vivianna M. Van Deerlin , Wayne W. Poon , Alison Goate , Vijay P. Singh , Bernie Devlin , Christiane Reitz , Ann C. McKee , Amanda Smith , Neill R. Graff-Radford , Walter A. Kukul , John Baillie , Andres Gelrud , Ranjan Duara , Thomas D. Bird , Clinton B. Wright , Deborah Blacker , Chiao-Feng Lin , Ge Li , Ronald C. Kim , Deborah C. Mash , Debby W. Tsuang , John P. Neoptolemos , Timothy B. Gardner , Kathryn L. Lunetta , Steven G. Younkin , Kara L. Hamilton-Nelson , Ronald L. Hamilton , F. Yesim Demirci , Eric M. Reiman , Charles DeCarli , John M Olichney , Richard Mayeux , Gregory A. Jicha , Michael R. O'Connell , Matt Tector , Eileen H. Bigio , Jonathan D. Glass , M. Ilyas Kamboh , Randall E. Brand , Christopher Lawrence , Steven E. Arnold , Jessica LaRusch , Elaine R. Peskind , David H. Cribbs , M.-Marsel Mesulam , Constantine G. Lyketsos , Michelle L. Kienholz , Frank M. LaFerla , Duane Beekly , Kelley Faber , Salvatore Spina , Gyungah Jun , Thiruvengadam Muniraj , Erik D. Roberson , Anna Karydas , Steven H. Ferris , Bruce L. Miller , Randall L. Woltjer , Li-San Wang , Lon S. Schneider , John C. Morris , John Q. Trojanowski , Jeffrey Kaye , Joseph E. Parisi , Nilufer Ertekin-Taner , Harry V. Vinters , Lidiya Orlichenko , Robert Barber , Chris E. Forsmark , Mary Sano , Bimaljit S. Sandhu , Peter A. Banks , Martin R. Farlow , Bradley T. Hyman , Joseph F. Quinn , Gary W. Beecham , James A. DiSario , Hakon Hakonarson , Daniel C. Marson , Adam C. Naj , Frank Martiniuk , Oscar L. Lopez , Mary E. Money , Julia Mayerle , William Greenhalf , Kathryn Roeder , Adam L. Boxer , Christine M. Hulette , Gerard D. Schellenberg , Georgios I. Papachristou , Douglas Galasko , James R. Burke , Donna B. Stolz , Murray A. Raskind , Peter Simon , Linda J. Van Eldik , Robert A. Hawes , Chang En Yu , Tatiana Foroud , Jonathan L. Haines , Stephen R. Wisniewski , William W. Seeley , Dhiraj Yadav , James J. Lah , C. Mel Wilcox , Sid Gilman , Liana G. Apostolova , Howard J. Rosen , Clinton T. Baldwin , Robert S. Stern , Narcis O. Zarnescu , Dennis W. Dickson , Margaret A. Pericak-Vance , Ashok Raj , Stephen T. Amann , Joseph D. Buxbaum , Ronald C. Petersen , Robert C. Green , David C. Whitcomb , Rudolph E. Tanzi , Lindsay A. Farrer , Helena C. Chui , Laura B. Cantwell , Wendy J. Mack , Samer Alkaade , Nigel J. Cairns , Thomas G. Beach , Frank Ulrich Weiss , Alyssa M. Krasinskas , Elizabeth Head , Nalini M. Guda , Julie A. Schneider , Malcolm B. Dick , Roger N. Rosenberg , Jill R. Murrel , Otto Valladares , Andrew J. Saykin , Huntington Potter , John R. Gilbert , Neil W. Kowall , Joseph Romagnuolo , Markus M. Lerch , Aimee Pierce , Roger L. Albin , John M. Ringman , James B. Leverenz , Carlos Cruchaga , Joshua W. Miller , Lei Yu , M. Michael Barmada , Lambertus Klei , Andrew P. Lieberman , Bernardino Ghetti , Robert Sutton , Kathleen A. Welsh-Bohmer , Juan C. Troncoso , Edward H. Koo , Elizabeth Crocco , Eden R. Martin , Daniel H. Geschwind , Regina M. Carney
المصدر:
Nature genetics
سنة النشر:
2012
مصطلحات موضوعية:
Male , Pancreatic disease , Pancreatitis, Alcoholic , Genome-wide association study , Biology , Article , 03 medical and health sciences , 0302 clinical medicine , Sex Factors , Gene Frequency , Genotype , Genetics , medicine , PRSS2 , Humans , Genetic Predisposition to Disease , Trypsin , Allele , Allele frequency , Homozygote , Genetic Variation , medicine.disease , 3. Good health , Hemizygote , 030220 oncology & carcinogenesis , Immunology , Claudins , Mutation , Trypsinogen , Pancreatitis , 030211 gastroenterology & hepatology , Female , Genome-Wide Association Study
الوصف:
Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 (P < 1 × 10(-12)) and X-linked CLDN2 (P < 1 × 10(-21)) through a two-stage genome-wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 cases and 4,170 controls). The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous in males) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07).
اللغة:
English
تدمد:
1546-1718
الوصول الحر:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f0af8515a19bbcd51602984c2eff7ecTest http://europepmc.org/articles/PMC3510344Test
حقوق:
OPEN
رقم الانضمام:
edsair.doi.dedup.....0f0af8515a19bbcd51602984c2eff7ec
قاعدة البيانات:
OpenAIRE
