Uloga alelnih varijanata MDR1 gena u patogenezi upalnih bolesti crijeva i odgovoru na liječenje glukokortikoidima
Bibliographic record
Abstract
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".