A comparative genetic study of tuberculosis and asthma susceptibility /
Notice bibliographique
Résumé
The worldwide rates of asthma have been increasing in the past twenty years, coinciding with a decreasing prevalence of tuberculosis in the major asthma endemic regions. The hygiene hypothesis proposes that in countries with better hygiene, reduced exposure to pathogens is responsible for the rising prevalence of allergic diseases. Mycobacterium tuberculosis , the cause of tuberculosis (TB), is thought to be a critical effector of the hygiene hypothesis since it can skew the immune system away from developing into an atopy associated immune profile. Hence, absence of exposure to M. tuberculosis might remove suppression of asthma development. Based on the hygiene hypothesis, we reasoned that genetic factors that predispose to TB should be protective for asthma/atopy and vice versa. Consequently, we tested genetic variants for (1) asthma risk based on known genetic effects in TB susceptibility, and (2) TB risk based on known genetic effects in asthma susceptibility. To identify genetic variants for asthma risk, we tested for nonrandom transmission of genetic variants of the Vitamin D Receptor (VDR) and the Natural Resistance Macrophage Protein 1 (NRAMP1) genes, two known TB susceptibility genes, in an asthma family-based cohort of French Canadian. To identify genetic variants for TB risk, we tested for distribution differences of genetic variants of several asthma associated genes: interleukin 4 (IL-4), IL-4 Receptor A (IL4RA), tumour necrosis factor A (TNFA ), lymphotoxin A (LTA) and VDR in TB cases and non-TB controls recruited in Mexico. Only VDR variants showed a risk modulating effect and where analyzed in more detail in the present thesis. In a North-Eastern Quebec asthma family-based cohort, of the 12 VDR variants tested 6 genetic variants located between intron 2 and 3' UTR we found to be strongly associated with asthma (0.0005 < p < 0.01) under an additive model. Haplotype specific genetic effects were also observed for asthma (0.0004 < p < 0.01). By contrast, no variants of the NRAMP1 gene were observed to be associated with asthma in this French Canadian asthma cohort. In the final set of experiments, I tested asthma associated genes for their impact on risk of TB disease. In a Mexican case-control study, 14 VDR variants tested, we observed 2 genetic variants at the 5' end of the gene to be associated (p < 0.05) with either susceptibility to TB, M. tuberculosis infection or disease progression. No associations were observed between genetic variants of IL4RA, TNFA and LTA, and TB or TB related phenotypes. These findings clearly identified VDR as asthma and TB susceptibility gene. However, since the genetic variants associated with asthma differ from those associated with TB it remains unclear how these variants influence the immune system to promote asthma but not TB, and vice versa. Although TB has been proposed as a suppressing force for asthma, other than VDR, we could not detect any genetic effect of TB susceptibility genes in the asthma study, nor effects of asthma susceptibility genes in the TB study. We interpret these findings as evidence against counter-selection of asthma and TB susceptibility gene variants.
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 | 0,001 | 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 | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».