Polymorphisms on rs9939609 FTO and rs17782313 MC4R genes in children and adolescent obesity: A systematic review

Resende, Cristina Maria Mendes; Silva, Helker Albuquerque Macedo da; Campello, Camilla Porto; Ferraz, Lívia Almeida Amaral; Lima, Elker Lene Santos de; Beserra, Maria Aparecida; Muniz, Maria Tereza Cartaxo; Silva, Lygia Maria Pereira da

doi:10.1016/j.nut.2021.111474

Cited by 16 publications

(8 citation statements)

References 31 publications

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“…The MC4R receptor is activated in the satiety state by the adrenocorticotropic hormone (ACTH) and the post-translational derivatives of POMC and the a-MSH, β-MSH, and γ-MSH neuropeptides; it is inhibited by orexigenic AgRP-mediated signaling, expressed in AgRP/NPY neurons in the arcuate nucleus [ 114 ]. The rs17782313 SNP is located 188 kb downstream of MC4R and has been strongly associated with the development of obesity in populations of different ethnicity and age, including children and adolescents [ 115 , 116 , 117 , 118 ]. Ligand-receptor changes could possibly contribute to the positive effect of the minor allele of rs17782313 SNP in BMI reduction in childhood obesity lifestyle interventions [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

The Genetic Basis of Childhood Obesity: A Systematic Review

2023

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Overweight and obesity in childhood and adolescence represents one of the most challenging public health problems of our century owing to its epidemic proportions and the associated significant morbidity, mortality, and increase in public health costs. The pathogenesis of polygenic obesity is multifactorial and is due to the interaction among genetic, epigenetic, and environmental factors. More than 1100 independent genetic loci associated with obesity traits have been currently identified, and there is great interest in the decoding of their biological functions and the gene–environment interaction. The present study aimed to systematically review the scientific evidence and to explore the relation of single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with changes in body mass index (BMI) and other measures of body composition in children and adolescents with obesity, as well as their response to lifestyle interventions. Twenty-seven studies were included in the qualitative synthesis, which consisted of 7928 overweight/obese children and adolescents at different stages of pubertal development who underwent multidisciplinary management. The effect of polymorphisms in 92 different genes was assessed and revealed SNPs in 24 genetic loci significantly associated with BMI and/or body composition change, which contribute to the complex metabolic imbalance of obesity, including the regulation of appetite and energy balance, the homeostasis of glucose, lipid, and adipose tissue, as well as their interactions. The decoding of the genetic and molecular/cellular pathophysiology of obesity and the gene–environment interactions, alongside with the individual genotype, will enable us to design targeted and personalized preventive and management interventions for obesity early in life.

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Section: Discussionmentioning

confidence: 99%

The Genetic Basis of Childhood Obesity: A Systematic Review

2023

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“…The FTO rs9939609 A allele was the first identified ( 14 ), and one of the most replicated genetic variants associated with elevated BMI and obesity in children ( 29 , 30 ). In contrast, our study found children with the A allele had lower BMI z -scores compared with children with the TT genotype.…”

Section: Discussionmentioning

confidence: 99%

The FTO rs9939609 Variant Is Associated with Cardiometabolic Disease Risk and Dietary Energy Intakes in Children with Mental Health Disorders

Wiedeman

Ngai

Henderson

et al. 2022

Current Developments in Nutrition

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Background Second-generation antipsychotics (SGAs) are used to treat children for mental health disorders but in some children cause cardiometabolic complications including weight gain and type 2 diabetes. Genetic variants may place a child at risk for developing these metabolic complications. The fat mass and obesity-associated (FTO) rs9939609 A allele has been associated with obesity and dietary energy intakes in healthy children but its relationship to metabolic complications in SGA-treated children is not known. Objective This study investigated the association of the FTO rs9939609 variant and SGA treatment with cardiometabolic complications and dietary intakes in children with mental health disorders. Design A cross-sectional population of children (≤18y;n = 506) with mental health disorders that were SGA-treated (n = 197) and SGA-naïve (n = 309) were recruited through the Department of Psychiatry at BC Children's Hospital. Dietary intakes were estimated using three-day food records in a subset of children (n = 73). Results Genotype frequencies were not different between SGA-treated (TT 42.6%, TA 38.6%, AA 18.8%) and SGA-naïve (TT 41.1%, TA 39.5%, AA 19.4%) children. Children with the A allele had lower BMI z-sores compared to the TT genotype (0.84±1.19 vs 1.19±1.36; P = 0.005, adjusted for ethnicity). We observed an interaction between FTO genotype and SGA status on fasting glucose (P = 0.036). SGA-naïve children with the A allele had higher fasting glucose than those with the TT genotype (4.96±0.35 vs 4.81±0.35 mmol/L;P = 0.001), in adjusted models (age, sex, ethnicity, and zBMI). This was not observed in SGA-treated children. Children with the A allele had higher daily total energy intakes compared to the TT genotype (1994±619 vs. 1814±484 kcal/d;P = 0.048), in adjusted models (age, sex, ethnicity, and zBMI; no effect of SGA-treatment was observed. Conclusion Our findings suggest the A allele of the FTO rs9939609 variant is associated with higher BMI in children with mental health disorders, but only in those not treated with SGAs.

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“…The same MC4R variant (rs17782313) and an FTO variant (rs9930506) were significantly associated with obesity in children, reported in multiple separate studies involving thousands of individual subjects, particularly Caucasians and Asians [ 29 ]. Further studies in children and adolescents with the same genes ( FTO and MC4R ) and variants were reported by Resende et al in a systematic review of the literature with an association with overweight and obesity [ 30 ].…”

Section: Obesity-related Genes and Defectsmentioning

confidence: 99%

Genetics of Obesity in Humans: A Clinical Review

Mahmoud

Kimonis

Butler

2022

IJMS

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Obesity is a complex multifactorial disorder with genetic and environmental factors. There is an increase in the worldwide prevalence of obesity in both developed and developing countries. The development of genome-wide association studies (GWAS) and next-generation sequencing (NGS) has increased the discovery of genetic associations and awareness of monogenic and polygenic causes of obesity. The genetics of obesity could be classified into syndromic and non-syndromic obesity. Prader–Willi, fragile X, Bardet–Biedl, Cohen, and Albright Hereditary Osteodystrophy (AHO) syndromes are examples of syndromic obesity, which are associated with developmental delay and early onset obesity. Non-syndromic obesity could be monogenic, polygenic, or chromosomal in origin. Monogenic obesity is caused by variants of single genes while polygenic obesity includes several genes with the involvement of members of gene families. New advances in genetic testing have led to the identification of obesity-related genes. Leptin (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), the melanocortin 4 receptor (MC4R), single-minded homolog 1 (SIM1), brain-derived neurotrophic factor (BDNF), and the neurotrophic tyrosine kinase receptor type 2 gene (NTRK2) have been reported as causative genes for obesity. NGS is now in use and emerging as a useful tool to search for candidate genes for obesity in clinical settings.

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Polymorphisms on rs9939609 FTO and rs17782313 MC4R genes in children and adolescent obesity: A systematic review

Cited by 16 publications

References 31 publications

The Genetic Basis of Childhood Obesity: A Systematic Review

The Genetic Basis of Childhood Obesity: A Systematic Review

The FTO rs9939609 Variant Is Associated with Cardiometabolic Disease Risk and Dietary Energy Intakes in Children with Mental Health Disorders

Genetics of Obesity in Humans: A Clinical Review

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