Uloga alelnih varijanata MDR1 gena u patogenezi upalnih bolesti crijeva i odgovoru na liječenje glukokortikoidima
Notice bibliographique
Résumé
Inflammatory bowel diseases are chronic diseases of unknown etiology and pathogenesis in which genetic factors contribute to development of disease. MDR1/ABCB1 is an interesting candidate gene in inflammatory bowel disease for several reasons. First, mdr1a knock out mice develop colitis that resembles ulcerative colitis. Second, it is located in the region of chromosome 7 associated with inflammatory bowel disease. Finally, high levels of its protein product Pgp, functioning as an ATP-dependant membrane efflux pump, are found on apical surfaces of intestinal epithelial cells. Initial reports confirmed association of polymorphisms of MDR1 and IBD. However, results of subsequent studies were contradictory making the role of MDR1 gene in IBD pathogenesis and susceptibility unclear. Additional interest in these gene arose from the fact that glucocorticoids are know substrates of Pgp. The fact that certain polymorphisms influence expression levels of Pgp leads to the possibility that different expression levels might influence outcome of glucocorticoid therapy. However, results of current studies are contradictory. Thus, the aims of this research were to investigate the association of MDR1polymorphisms and inflammatory bowel disease and to investigate the association of these polymorphisms with certain clinical characteristics. We also aimed to investigate the association of MDR1 polymorphisms with outcome of glucocorticoid therapy with an attempt to identify aleles or genotypes risk conffering for therapy failure. \nA total of 310 inflammatory bowel disease patients, 199 Crohn's disease and 109 ulcerative colitis patients, and 120 healthy controls were included in the study. All subjects were genotyped for G2677T/A i C3435T polymorphism using RT-PCR. In IBD patients review of medical records was performed and patients were meticulously phenotyped according to the Montreal classification. Additionaly, data regarding exposure to glucocorticoids and therapy outcome were recorded and patients were categorised as having good response, dependant or refractory to glucocorticoids. \nWe report association of MDR1 gene polymorphisms and inflammatory bowel disease on the level of alleles, genotypes and two locus haplotypes. Based on our findings, the observed association of MDR1 polymorphisms and IBD is modest. We also report an association of investigated polymorphisms and phenotypic characteristics of Crohn's disease patients. Furthermore, we found an association with outcome of glucocorticoid therapy. The observed effect is also modest but is somewhat more prononced in ulcerative colitis patients. \nIn conclusion, MDR1 gene polymorphisms are associated with inflammatory bowel disease. Apart from their effect on disease susceptibility they also exhibit a disease-modifying effect in Crohn's disease. Furthermore, MDR1 gene has a modest impact glucocorticoid therapy outcome that is more pronounced in ulcerative colitis.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».