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- Gianfagna, Francesco, et al.
(författare)
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The role of neuromedin U in adiposity regulation. Haplotype analysis in European children from the IDEFICS Cohort.
- 2017
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Neuromedin U (NMU) is a hypothalamic neuropeptide with important roles in several metabolic processes, recently suggested as potential therapeutic target for obesity. We analysed the associations between NMU gene variants and haplotypes and body mass index (BMI) in a large sample of European children.From a large European multi-center study on childhood obesity, 4,528 children (2.0-9.9 years, mean age 6.0±1.8 SD; boys 52.2%) were randomly selected, stratifying by age, sex and country, and genotyped for tag single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653,C:T) of NMU gene, then haplotypes were inferred. Regression models were applied to estimate the associations between SNPs or haplotypes and BMI as well as other anthropometric measures. BMI was associated with all NMU SNPs (p<0.05). Among five haplotypes inferred, the haplotype carrying the minor alleles (CCT, frequency = 22.3%) was the only associated with lower BMI values (beta = -0.16, 95%CI:-0.28,-0.04, p = 0.006; z-score, beta = -0.08, 95%CI:-0.14,-0.01, p = 0.019) and decreased risk of overweight/obesity (OR = 0.81, 95%CI:0.68,0.97, p = 0.020) when compared to the most prevalent haplotype (codominant model). Similar significant associations were also observed using the same variables collected after two years' time (BMI, beta = -0.25, 95%CI:-0.41,-0.08, p = 0.004; z-score, beta = -0.10, 95%CI:-0.18,-0.03, p = 0.009; overweight/obesity OR = 0.81, 95%CI:0.66,0.99, p = 0.036). The association was age-dependent in girls (interaction between CCT haplotypes and age, p = 0.008), more evident between 7 and 9 years of age. The CCT haplotype was consistently associated with lower levels of fat mass, skinfold thickness, hip and arm circumferences both at T0 and at T1, after adjustment for multiple testing (FDR-adjusted p<0.05).This study shows an association between a NMU haplotype and anthropometric indices, mainly linked to fat mass, which appears to be age- and sex-specific in children. Genetic variations within or in linkage with this haplotype should be investigated to identify functional variants responsible for the observed phenotypic variation.
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| 2. |
- Gianfagna, Francesco, et al.
(författare)
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Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children.
- 2013
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Neuromedin U, encoded by the NMU gene, is a hypothalamic neuropeptide that regulates both energy metabolism and bone mass. The beta-2 adrenergic receptor, encoded by the ADRB2 gene, mediates several effects of catecholamine hormones and neurotransmitters in bone. We investigated whether NMU single nucleotide polymorphisms (SNPs) and haplotypes, as well as functional ADRB2 SNPs, are associated with bone stiffness in children from the IDEFICS cohort, also evaluating whether NMU and ADRB2 interact to affect this trait. A sample of 2,274 subjects (52.5% boys, age 6.2±1.8 years) from eight European countries, having data on calcaneus bone stiffness index (SI, mean of both feet) and genotyping (NMU gene: rs6827359, rs12500837, rs9999653; ADRB2 gene: rs1042713, rs1042714), was studied. After false discovery rate adjustment, SI was significantly associated with all NMU SNPs. rs6827359 CC homozygotes showed the strongest association (recessive model, Δ=-1.8, p=0.006). Among the five retrieved haplotypes with frequencies higher than 1% (range 2.0-43.9%), the CCT haplotype (frequency=39.7%) was associated with lower SI values (dominant model, Δ=-1.0, p=0.04) as compared to the most prevalent haplotype. A non-significant decrease in SI was observed in in ADRB2 rs1042713 GG homozygotes, while subjects carrying SI-lowering genotypes at both SNPs (frequency=8.4%) showed much lower SI than non-carriers (Δ=-3.9, p<0.0001; p for interaction=0.025). The association was more evident in preschool girls, in whom SI showed a curvilinear trend across ages. In subgroup analyses, rs9999653 CC NMU or both GG ADRB2 genotypes were associated with either lower serum calcium or β-CrossLaps levels (p=0.01). This study in European children shows, for the first time in humans, a role for NMU gene through interaction with ADRB2 gene in bone strength regulation, more evident in preschool girls.
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| 3. |
- Grippi, Claudio, et al.
(författare)
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Association between variants of neuromedin U gene and taste thresholds and food preferences in European children: Results from the IDEFICS study.
- 2019
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Ingår i: Appetite. - : Elsevier BV. - 1095-8304 .- 0195-6663. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide neuromedin U (NMU) known for its role in appetite, feeding and energy balance could be involved in the control of food choice and taste sensitivity. We examined the association between NMU polymorphisms/haplotypes and taste thresholds and food preferences in a population of European children.A total of 578 subjects from the IDEFICS study (mean age 7.5±0.8 SD, boys 53.6%) with NMU genotype data and food preference (salty, fatty, sweet, flavour and umami food) and taste threshold (salt, fat, sweet, umami) tests available were analysed. Three single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653, C:T) of NMU gene were analyzed and five major haplotypes were inferred. The associations between genotypes and food preferences or taste thresholds were investigated (odds ratios -OR, adjusted for age, sex and country). A p<0.05 after false discovery rate adjustment (pFDR) was considered statistically significant.The association between NMU genotypes and food preference showed two NMU SNPs associated with preference for food containing sodium glutamate (umami taste; rs6827359C, OR=1.61, 95% confidence interval (CI):1.20-2.17; rs9999653T, OR=1.59, 95%CI:1.18-2.13). In the haplotype analysis, the CTT haplotype showed an OR of 1.70 (95%CI:1.16-2.5) for the umami food preference, while CCT haplotype showed an OR of 1.63 (95%CI:1.11-2.40), compared to the most frequent haplotype (TTC). Carriers of CCT/CCT vs subjects with no CCT haplotype showed an OR of 4.78 (95%CI:1.86-12.30). Umami food preference was associated with low values of BMI z-score, arm circumferences, skinfolds and fat mass (pFDR<0.05). No association between NMU genetic variants and taste thresholds was found.This study shows for the first time in children an association between preference for umami food and a NMU haplotype, previously found associated with low BMI values.
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