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Article

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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Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
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Department of Medicine, Sleep Center of Excellence, Columbia University Irving Medical Center, New York, NY 10032, USA
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Department of Computer Languages and Systems, Universitat Jaume I, 12071 Castellón, Spain
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Department of Internal Medicine, Hospital Clinic, Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Villarroel, 170, 08036 Barcelona, Spain
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CIBER Cáncer, Instituto de Salud Carlos III, 28029 Madrid, Spain
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Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA
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Precision Nutrition and Obesity Program, IMDEA Alimentación, 28049 Madrid, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2020, 12(11), 3323; https://doi.org/10.3390/nu12113323
Received: 3 September 2020 / Revised: 21 October 2020 / Accepted: 24 October 2020 / Published: 29 October 2020
(This article belongs to the Section Nutrigenetics and Nutrigenomics)
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. View Full-Text
Keywords: melatonin receptor; fasting glucose; type-2 diabetes; MTNR1B polymorphism; age-interaction; heterogeneity; Mediterranean population; pregnancy; gestational diabetes; women melatonin receptor; fasting glucose; type-2 diabetes; MTNR1B polymorphism; age-interaction; heterogeneity; Mediterranean population; pregnancy; gestational diabetes; women
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MDPI and ACS Style

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/nu12113323

AMA Style

Sorlí JV, Barragán R, Coltell O, Portolés O, Pascual EC, Ortega-Azorín C, González JI, Estruch R, Saiz C, Pérez-Fidalgo A, Ordovas JM, 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(11):3323. https://doi.org/10.3390/nu12113323

Chicago/Turabian Style

Sorlí, Jose V., Rocío Barragán, Oscar Coltell, Olga Portolés, Eva C. Pascual, Carolina Ortega-Azorín, José I. González, Ramon Estruch, Carmen Saiz, Alejandro Pérez-Fidalgo, Jose M. Ordovas, and Dolores Corella. 2020. "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 12, no. 11: 3323. https://doi.org/10.3390/nu12113323

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