Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-31
pubmed:abstractText
Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-10381903, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-10801865, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-10835640, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-11097832, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-12709065, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-13679035, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-15297300, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-28765, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-508771, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-6969677, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-8650574, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-8683601, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-8841182, http://linkedlifedata.com/resource/pubmed/commentcorrection/16699518-9504803
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1061-4036
pubmed:author
pubmed-author:FriessHelmutH, pubmed-author:LerchMarkus MMM, pubmed-author:SimonPeterP, pubmed-author:KukorZoltánZ, pubmed-author:Sahin-TóthMiklósM, pubmed-author:MalatsNúriaN, pubmed-author:RealFrancisco XFX, pubmed-author:AkarNejatN, pubmed-author:WiedenmannBertramB, pubmed-author:PignattiPier FrancoPF, pubmed-author:MacekMilanMJr, pubmed-author:FérecClaudeC, pubmed-author:KähneThiloT, pubmed-author:HalangkWalterW, pubmed-author:NickelRenateR, pubmed-author:TeichNielsN, pubmed-author:OckengaJohannJ, pubmed-author:KeimVolkerV, pubmed-author:LandtOlfertO, pubmed-author:WittHeikoH, pubmed-author:BeckerMichaelM, pubmed-author:BhatiaEeshE, pubmed-author:PfützerRolandR, pubmed-author:SchmidtHartmutH, pubmed-author:MoralPedroP, pubmed-author:SchulzHans-UlrichHU, pubmed-author:Destro-BisolGiovanniG, pubmed-author:SpediniGabriellaG, pubmed-author:RohdeKlausK, pubmed-author:ChenJian-MinJM, pubmed-author:KageAndreasA, pubmed-author:BergThomasT, pubmed-author:TruningerKasparK, pubmed-author:AmmannRudolf WRW, pubmed-author:BraunMarkusM, pubmed-author:LöhrMatthiasM, pubmed-author:EibergHansH, pubmed-author:SpicakJuliusJ, pubmed-author:WeissFrank UlrichFU, pubmed-author:CastellaniCarloC, pubmed-author:CavestroGiulia MartinaGM, pubmed-author:JansenJan B M JJB, pubmed-author:GressThomas MTM, pubmed-author:SzepessyEditE, pubmed-author:Le MaréchalCédricC, pubmed-author:LuckWernerW, pubmed-author:RosendahlJonasJ, pubmed-author:RickardsOlgaO, pubmed-author:HalangkJulianeJ, pubmed-author:KoudovaMonikaM, pubmed-author:BargetziMarioM, pubmed-author:KeilThomasT, pubmed-author:BöckWolfgangW, pubmed-author:DahmStefanS, pubmed-author:CernyMilosM, pubmed-author:DrenthJoost PhJP, pubmed-author:RausovaEvaE, pubmed-author:MenzelHans-JürgenHJ, pubmed-author:GalavottiRobertaR, pubmed-author:ZarnescuNarcis OctavianNO, pubmed-author:GronebergDavid AlexanderDA, pubmed-author:BernardovaJanaJ, pubmed-author:GüldnerClaudiaC
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