Identification and chromosomal localization of ecogenetic components of electrolyte excretion
Notice bibliographique
Résumé
OBJECTIVE: To determine to what extent urinary excretion of blood pressure-modulating electrolytes is genetically determined, and to identify their chromosomal localization. DESIGN AND METHODS: Twenty-six rat recombinant inbred strains (RIS) originating from reciprocal crosses of normotensive Brown Norway (BN.Lx) and spontaneously hypertensive rats (SHR) were used. A pilot experiment on a subset of strains determined that fasting decreases the impact of environmental noise and increases that of heritability. Twenty-four-hour urinary collections were obtained from fasting rats aged 6-12 weeks (3-8 rats per strain). Sodium (Na), potassium (K) and calcium (Ca) excretions were measured, and the Na/K ratio calculated. These phenotypes served as quantitative traits for the search of quantitative trait loci (QTLs) by scanning the RIS genome that was mapped with 475 polymorphic markers. RESULTS: Constant Na intake resulted in a low heritability for Na excretion, reflecting the environmental impact (intake = excretion), whereas fasting revealed a gradient among RIS indicative of the genetic component of the traits. In the fasting state, a locus on chromosome 14 was found to be significantly associated with K excretion (Alb, P = 0.00002, r = -0.69, logarithm of the odds score (LOD) 3.9), whereas another locus on chromosome 10 (D10Cebrp97s5, P = 0.0003, r = -0.69, LOD 3.0) and one on chromosome 6 (D6Cebrp97s14, P = 0.0007, r = -0.65, LOD 1.9) were more significantly associated with Na excretion and the Na/K ratio respectively. The observed correlations were all negative for Na, K and Na/K, indicating a higher excretion of Na and K and a greater Na/K ratio in rats bearing BN.Lx alleles at these loci, i.e. salt retention in fasting SHR. These three loci accounted for 47-55% of variance of their associated trait, suggesting that they are the main genetic determinants for these phenotypes in basal fasting conditions. Rats bearing the Y chromosome of SHR origin had significantly higher K excretion that, in turn, led to a significantly lower Na/K ratio. Finally, a locus on chromosome 7 was linked to Ca excretion, explaining 46% of the trait variance (D7Mit10, LOD score 3.0). CONCLUSION: RIS enabled us to determine QTLs for environmentally modulated traits such as Na, K and Ca excretions. We demonstrated that whereas urinary electrolytes are determined mainly by intake (environment) in a steady state, their excretion in an adaptive state (fasting) is predominantly genetically determined by distinct QTL on autosomes as well as the Y chromosome. Furthermore, the loci responsible for Na and K excretions act independently of the locus governing the relative excretion of Na/K. Thus, the salt-retaining aspects of some hypertensives may be, in large part, determined by genes responsible for renal excretion, the impact of which is predominant over the environment under acute challenge.
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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 ».