Candidate Gene Polymorphisms and Their Association with TCD Velocities in Children with Sickle Cell Disease.
Notice bibliographique
Résumé
Abstract Ischemic stroke occurs in 11% of patients with sickle cell disease (SCD) by age 20. The STOP and STOP-II trials showed that the risk of ischemic stroke increases with Transcranial Doppler (TCD) velocities in major intracranial arteries in children with SCD 2–16 years of age, and that the risk in children with abnormal velocities (>200 cm/sec) can be significantly reduced by prophylactic transfusions. Risk factors for development of high TCD phenotype are not clearly established. In an ancillary study to STOP/STOP-II, we analyzed 28 polymorphisms in 20 candidate genes for association with elevated TCD velocity. DNA was extracted from 130 patients randomized in the STOP trial, all of whom had abnormal TCD velocities, and from 355 patients who were screened for STOP II at 8 participating centers. None of the subjects from either trial had histories of overt stroke when they were screened. Samples from STOP subjects were anonymized according to an IRB-approved plan; informed consent/assent was obtained from subjects screened for the STOP-II trial. Hb phenotype was ascertained by HPLC. High throughput genotyping was performed using the MassARRAY™ System (Sequenom Inc., San Diego, CA) at Mass U. TCD status was classified as normal (<170 cm/sec) or not normal (>170 cm/sec) using the average of all TCDs on each patient, excluding any TCDs obtained after starting transfusion (median: 2 TCD exams, range 1–16). Genotyping results for each SNP were also reduced to a binary classification (mutation present or absent) by combining heterozygous subjects with those homozygous for the mutation. Conditional logistic regression was employed to model the probability of having at least 1copy of the mutant allele as a function of TCD status stratified on age class. Under this approach, the odds ratio (OR) relating TCD status to genotype is assumed to be the same at all ages but the prevalence of abnormal or conditional TCD is allowed to vary with age. Seven SNPs were excluded from analyses: all subjects studied (479) were homozygous for the common allele for 5 SNPs, and only 2 subjects were heterozygous for the minor allele for 2 SNPs. The prevalence of abnormal TCD varied with age; the highest prevalence was found in 8–9 year old subjects. Only one SNP, VCAM G1238C, had a significant OR of 0.6 (p=0.03) suggesting this SNP is protective from high TCD. The same polymorphism was found to be protective from stroke with an OR of 0.3 in a different cohort of patients by Taylor et al (Blood, 100:4303–9, 2002). Several published studies have reported on association of stroke with candidate gene polymorphisms with differing results. This is the first large scale study of the association of abnormal TCD (stroke risk) with genetic polymorphisms. To our knowledge, it is also the first confirmatory genetic association study in SCD and cerebrovascular disease in a different population of subjects. Functional analyses of this polymorphism and association of stroke and candidate gene polymorphisms in this cohort are planned.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 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) | 0,000 | 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 tête enseignante, 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 ».