An exploration of the contribution of paraoxonase 1 genetic variants, homocysteine, and nutritional factors on the risk of small-for-gestational age birth
Notice bibliographique
Résumé
Small-for-gestational age (SGA) births are defined as babies who are born at less than the 10th percentile of weight for their sex and gestational age based on population growth standards1. SGA babies may be at risk for type II diabetes, cardiovascular disease, and hypertension later in life, although the exact biological mechanisms behind SGA birth are not fully understood1. Paraoxonase 1 (PON1) genetic variants are known to influence the ability of PON1 enzymes to prevent oxidative damage by hydrolyzing phospholipids, lipid peroxide by-products, and amino acid by-products such as homocysteine (Hcy)2. Infante-Rivard has previously shown that PON1 polymorphisms and Hcy concentrations (albeit in an unexpected protective direction for the latter) are associated with SGA birth3-4, however, their joint contribution to the risk of SGA birth has not been studied. The objective of this thesis is to explore the gene-environment interactions between three functional PON1 variants and plasma Hcy concentrations as well as food folate consumption (lentils) and folic acid vitamin supplementation on the risk of SGA birth. The present study uses data from births of infants at a university hospital in Montreal, Quebec. 493 case mothers and 472 control mothers provided informed consent to participate in the study. Cases were SGA babies born from May 1998 to June 2000, and controls were appropriate-for-gestational-age (AGA) babies born at the same hospital during the same time period4. Three PON1 genetic variants were analyzed in this study (C108T, L55M and Q192R). Information regarding Hcy concentrations and nutritional variables such as lentil and folate-containing vitamin consumption was collected and analyzed. Case-control, case-only and case-parent trio study designs were used and the data analyzed using unconditional logistic regression and Poisson log-linear models.Results indicate that mothers with wild type PON1 108CC genotypes and high Hcy concentrations (≥ 90th percentile) may be protected against SGA birth compared to those with lower Hcy concentrations (<90th percentile) after adjustment for gestational age, sex of the fetus, and ethnicity (OR=0.52, 95% CI [0.25, 1.05]). This effect was shown to be similar for the PON1 L55M polymorphism, in both maternal and fetal models. Individuals with the PON1 55MM genotype and high Hcy levels were shown to be at an increased risk of SGA birth compared to those with low Hcy levels after adjustment for the same covariates (maternal model, OR=1.38, 95% CI [0.46, 4.17]). Results from case-only and case-parent trio designs generally concur with those of the case-control study design. PON1 polymorphisms appear to modify the effect of Hcy on the risk of SGA birth; however, the results of this study are generally non-significant and more work is needed to characterize this relationship as well as the biological mechanism behind this effect.
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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 ».