Intestinal permeability and Genetic determinants in patients,first degree relatives,and controls in a High incidence area's of Crohn's disease in Southern Italy

Mario Cottone, Antonella Raso, Anna Mattaliano, Maria A. Lo Presti, Maria R. Giofré, Walter Fries, Angelo Macaluso

Risultato della ricerca: Articlepeer review

55 Citazioni (Scopus)

Abstract

1. Am J Gastroenterol. 2005 Dec;100(12):2730-6.Intestinal permeability and genetic determinants in patients, first-degreerelatives, and controls in a high-incidence area of Crohn's disease in SouthernItaly.Fries W, Renda MC, Lo Presti MA, Raso A, Orlando A, Oliva L, Giofré MR, Maggio A,Mattaliano A, Macaluso A, Cottone M.Dipartimento di Medicina Interna e Terapia Medica, Università di Messina,Messina, Italy.OBJECTIVE: A defect of gastrointestinal barrier function is considered torepresent an important step in the pathogenesis of Crohn's disease (CD) but themechanisms leading to an increased intestinal permeability (IP) are poorlyunderstood. Since IP is influenced by pro-inflammatory mediators, it seems likelythat a genetically determined abnormal immune response may lead to a loss ofbarrier function.METHODS: In a geographic area in Southern Italy with high incidence of CD weinvestigated IP (lactulose/mannitol testing) together with the three mainmutations of the NOD2/CARD15 and the D299G polymorphism of the toll-like receptor(TLR)-4 gene in 23 families of CD patients (patients and first-degree relatives).RESULTS: Forty-eight percent of CD patients and 40% of their healthy relativeswere found to have an abnormal IP compared to 5% of an appropriate controlpopulation (p < 0.0001). IP, however, was not associated with the L1007finsCmutation of the NOD2/CARD15 or the D299G variant of the TLR-4 gene. Allelefrequency of the only L1007finsC mutation of CARD15 was significantly increasedin patients (8.7%, p < 0.003) and in relatives (8.3%, p < 0.024) compared withcontrols (2.4%), whereas the D299G variant of the TLR-4 gene was found to beincreased only in relatives (8.3%, p < 0.022), but not in patients (4.3%)compared with the control population (1.7%).CONCLUSIONS: There was no association between IP and genetic markers. Ourfindings showed a very high proportion of healthy first-degree relatives to bare alterations suggested to constitute determinants of CD. Mutations of NOD2/CARD15 or TLR-4, however, do not lead to permeability defects emphasizing the importanceof additional environmental and/or genetic factors for pathogenesis.PMID: 16393227 [PubMed - indexed for MEDLINE]
Lingua originaleEnglish
pagine (da-a)2730-2736
Numero di pagine7
RivistaAmerican Journal of Gastroenterology
Volume100
Stato di pubblicazionePublished - 2005

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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