Abstract
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.
Highlights
There is renewed interest in research into precision nutrition [1,2], an example being the initiative carried out by the National Institutes of Health (NIH) within the 2020–2030 Strategic Plan [3].This Plan stresses the need for research into “when”
We retrospectively explored the interaction between the number of full-term pregnancies reported by women and the melatonin receptor 1B (MTNR1B) polymorphism in the future type-2 diabetes risk
The association of the MTNR1B-rs10830963 polymorphism with fasting glucose was analyzed in 1378 subjects from the general population (OBENUTIC study)
Summary
There is renewed interest in research into precision nutrition [1,2], an example being the initiative carried out by the National Institutes of Health (NIH) within the 2020–2030 Strategic Plan [3].This Plan stresses the need for research into “when”. There is renewed interest in research into precision nutrition [1,2], an example being the initiative carried out by the National Institutes of Health (NIH) within the 2020–2030 Strategic Plan [3]. It is assumed that the effect of genetic polymorphisms, mainly single nucleotide polymorphisms (SNPs), is the same regardless of the age group analyzed. This can give rise to various biases and a lack of replication of associations on comparing some studies with others when they have been carried out using very different age groups
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