Chronological age interacts with the circadian melatonin receptor 1b gene variation, determining fasting glucose concentrations in mediterranean populations. Additional analyses on type-2 diabetes risk
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Otros documentos de la autoría: Sorlí, José V; Barragán-Arnal, Rocío; Coltell, Oscar; Portolés, Olga; Pascual, Eva C.; CAROLINA, ORTEGA-AZORÍN; González, José I.; Estruch, Ramon; Saiz, Carmen; Pérez-Fidalgo, J. Alejandro; Ordovas, Jose; Corella, Dolores
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Título
Chronological age interacts with the circadian melatonin receptor 1b gene variation, determining fasting glucose concentrations in mediterranean populations. Additional analyses on type-2 diabetes riskAutoría
Fecha de publicación
2020-11-01Editor
MDPIISSN
2072-6643Cita bibliográfica
Sorlí, J.V.; Barragán, R.; Coltell, O.; Portolés, O.; Pascual, E.C.; Ortega-Azorín, C.; González, J.I.; Estruch, R.; Saiz, C.; Pérez-Fidalgo, A.; Ordovas, J.M.; Corella, D. Chronological Age Interacts with the Circadian Melatonin Receptor 1B Gene Variation, Determining Fasting Glucose Concentrations in Mediterranean Populations. Additional Analyses on Type-2 Diabetes Risk. Nutrients 2020, 12, 3323. https://doi.org/10.3390/nu12113323Tipo de documento
info:eu-repo/semantics/articleVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Gene-age interactions have not been systematically investigated on metabolic phenotypes
and this modulation will be key for a better understanding of the temporal regulation in nutrigenomics.
Taking into account ... [+]
Gene-age interactions have not been systematically investigated on metabolic phenotypes
and this modulation will be key for a better understanding of the temporal regulation in nutrigenomics.
Taking into account that aging is typically associated with both impairment of the circadian system
and a decrease in melatonin secretion, we focused on the melatonin receptor 1B (MTNR1B)-rs10830963
C>G variant that has been associated with fasting glucose concentrations, gestational diabetes,
and type-2 diabetes. Therefore, our main aim was to investigate whether the association between the
MTNR1B-rs10830963 polymorphism and fasting glucose is age dependent. Our secondary aims were
to analyze the polymorphism association with type-2 diabetes and explore the gene-pregnancies
interactions on the later type-2 diabetes risk. Three Mediterranean cohorts (n = 2823) were analyzed.
First, a cross-sectional study in the discovery cohort consisting of 1378 participants (aged 18 to
80 years; mean age 41 years) from the general population was carried out. To validate and extend
the results, two replication cohorts consisting of elderly individuals were studied. In the discovery
cohort, we observed a strong gene-age interaction (p = 0.001), determining fasting glucose in such
a way that the increasing effect of the risk G-allele was much greater in young (p = 5.9 × 10−10)
than in elderly participants (p = 0.805). Consistently, the association of the MTNR1B-rs10830963
polymorphism with fasting glucose concentrations in the two replication cohorts (mean age over
65 years) did not reach statistical significance (p > 0.05 for both). However, in the elderly cohorts,
significant associations between the polymorphism and type-2 diabetes at baseline were found.
Moreover, in one of the cohorts, we obtained a statistically significant interaction between the MTNR1B polymorphism and the number of pregnancies, retrospectively assessed, on the type-2
diabetes risk. In conclusion, the association of the MTNR1B-rs10830963 polymorphism with fasting
glucose is age-dependent, having a greater effect in younger people. However, in elderly subjects,
associations of the polymorphism with type-2 diabetes were observed and our exploratory analysis
suggested a modulatory effect of the number of past pregnancies on the future type-2 diabetes
genetic risk. [-]
Publicado en
Nutrients Vol.12, Núm.11, Pág.1-20, Article Núm.3323Entidad financiadora
Generalitat Valenciana | Fundació La Marató de TV3 | Instituto de Salud Carlos III | Ministerio de Economía y Competitividad- Fondo Europeo de Desarrollo Regional (FEDER) | Universitat Jaume I | Premis Rei Jaume I d'investigació mèdica 2018 | US Department of Agriculture
Proyecto de investigación
PROMETEO2017/017APOSTD/2019/136
538/U/2016
CIBER 06/03
PI06/1326
PI13/00728
PI16/00366
PI19/00781
SAF2016–80532-R
P1–1B2013–54
COGRUP/2016/06
8050–51000-098-00D
Derechos de acceso
Creative Commons - Attribution (BY)
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