Evidence from a meta-analysis for association of MC4R rs17782313 and FTO rs9939609 polymorphisms with susceptibility to obesity in children

Dastgheib, Seyed Alireza; Bahrami, Reza; Setayesh, Sepideh; Salari, Seyedali; Mirjalili, Seyed Reza; Noorishadkam, Mahmood; Sadeghizadeh‐Yazdi, Jalal; Akbarian, Elahe; Neámatzadeh, Hossein

doi:10.1016/j.dsx.2021.102234

Cited by 24 publications

(19 citation statements)

References 49 publications

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“…The same MC4R variant and FTO variant were found to be significantly associated with obesity in children reported in multiple separate studies involving thousands of individual subjects, particularly in Caucasians and Asians. [ 37 ] Further studies in children and adolescents with the same genes (FTO and MC4R) and variants were reported by Resende et al. [ 38 ] in a systematic review of literature from an association with overweight and obesity.…”

Section: Introductionmentioning

confidence: 87%

Syndromic and Nonsyndromic Obesity: Underlying Genetic Causes in Humans

Duis

Butler

2022

Advanced Biology

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cardiovascular disease, hypertension, cancers, orthopedic problems, and reduced fertility.Genetic factors can be classified as monogenic or caused by variants of single genes, polygenic involving several interacting genes, or syndromes accompanying obesity and recognized phenotypes. Neurological dysfunction or abnormal regulation of energy utilization, expenditure or storage via hormone production, transport or receptors impact overall energy homeostasis. [1,2] Furthermore, heritability estimates indicate that genetic factors may contribute to up to 70% of obesity, primarily affecting genetic pathways common in lipid metabolism, fat deposition or lipid transport, eating behavior, food selection and hormones, physical activity or energy expenditure based on studies from monozygotic twins reared apart and living in a different environment. [3] Heritability estimates do increase from infancy through adolescence. Over 10 000 references in the medical literature were identified when searching for obesity genes and syndromes with approximately 80 recorded obesityrelated syndromes. [1][2][3][4][5] The prevalence estimates for monogenic obesity syndromes range from about one in 550 to aprroximately one in 1 million. [5] Clinical findings identified in genetic obesity syndromes often overlap, as found in at least 52 related obesity syndromes displaying some form of intellectual disability while seven syndromes present with macrocephaly and seven syndromes with microcephaly. [5] Obesity syndromes may exhibit complex patterns of inheritance including autosomal dominant (e.g., Alstrom), autosomal recessive (e.g., Carpenter), X-linked (e.g., Borjeson-Forssman-Lehmann), errors in genomic imprinting (e.g., Prader-Willi), triallelic inheritance (e.g., Bardet-Biedel) or chromosome anomalies (e.g., 16p11.2 deletion). Hormonal Pathways and Genetic RegulationHormones and their role in appetite control and weight regulation are now an active area of research with clinical trials often focusing on hyperphagia and overeating, common in rare obesity-related disorders such as Prader-Willi syndrome. [6] Eating hormones are becoming increasingly recognized as playing a role in the central nervous system (CNS), particularly regions Growing evidence supports syndromic and nonsyndromic causes of obesity, including genome-wide association studies, candidate gene analysis, advanced genetic technology using next-generation sequencing (NGS), and identification of copy number variants. Identification of susceptibility genes impacts mechanistic understanding and informs precision medicine. The cause of obesity is heterogeneous with complex biological processes playing a role by controlling peptides involved in regulating appetite and food intake, cellular energy, and metabolism. Evidence for heritability shows genetic components contributing to 40%-70% of obesity. Monogenic causes and obesity-related syndromes are discussed and illustrated as well as biological pathways, gene interactions, and factors contributing to the obesity phenotype. Over 550...

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Section: Introductionmentioning

confidence: 87%

Syndromic and Nonsyndromic Obesity: Underlying Genetic Causes in Humans

Duis

Butler

2022

Advanced Biology

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“…Additional studies by Castro et al on four obesity-related genes ( PPARG -rs1801282; PPARGC1A -rs8192678; FTO -rs9939609; MC4R -rs17782313) showed that three of the four genes ( PPARG, FTO, MC4R ) had a combined effect on overweight and obesity at an odds ratio of 1.65 ( p = 0.008) in a large case-control study in the Brazilian population [ 28 ]. 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%

“…Dastgheib et al performed a metanalysis involving 13 studies with 9565 cases and 11,956 controls on MC4R rs17782313 and 18 studies with 4789 cases and 15,918 controls on FTO rs9939609. They found that odds ratios showed significant results indicating that these variants were associated with a higher risk of obesity [ 29 ].…”

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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“…Other two FTO gene variants, the rs8050136 and the rs1421085, were found associated to obesity traits in different children population studies alone or in combination to the best investigated rs9939609 variant ( 67 , 70 – 72 ). Although, the true role of these additional loci remain unknown, deserving further investigations in the next future, a very recent meta-analysis reported this and other variants in FTO genes and their association with pediatric obesity overall ( 73 ). Often FTO variants have been investigated with variants in the MC4R of which mutations can be positioned between monogenic obesity and the polygenic obesity ( 36 , 73 , 74 ).…”

Section: Genetics Of Pediatric Obesitymentioning

confidence: 99%

Genetics, epigenetics and transgenerational transmission of obesity in children

et al. 2022

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Sedentary lifestyle and consumption of high-calorie foods have caused a relentless increase of overweight and obesity prevalence at all ages. Its presently epidemic proportion is disquieting due to the tight relationship of obesity with metabolic syndrome and several other comorbidities which do call for urgent workarounds. The usual ineffectiveness of present therapies and failure of prevention campaigns triggered overtime a number of research studies which have unveiled some relevant aspects of obesity genetic and epigenetic inheritable profiles. These findings are revealing extremely precious mainly to serve as a likely extra arrow to allow the clinician’s bow to achieve still hitherto unmet preventive goals. Evidence now exists that maternal obesity/overnutrition during pregnancy and lactation convincingly appears associated with several disorders in the offspring independently of the transmission of a purely genetic predisposition. Even the pre-conception direct exposure of either father or mother gametes to environmental factors can reprogram the epigenetic architecture of cells. Such phenomena lie behind the transfer of the obesity susceptibility to future generations through a mechanism of epigenetic inheritance. Moreover, a growing number of studies suggests that several environmental factors such as maternal malnutrition, hypoxia, and exposure to excess hormones and endocrine disruptors during pregnancy and the early postnatal period may play critical roles in programming childhood adipose tissue and obesity. A deeper understanding of how inherited genetics and epigenetics may generate an obesogenic environment at pediatric age might strengthen our knowledge about pathogenetic mechanisms and improve the clinical management of patients. Therefore, in this narrative review, we attempt to provide a general overview of the contribution of heritable genetic and epigenetic patterns to the obesity susceptibility in children, placing a particular emphasis on the mother-child dyad.

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Evidence from a meta-analysis for association of MC4R rs17782313 and FTO rs9939609 polymorphisms with susceptibility to obesity in children

Cited by 24 publications

References 49 publications

Syndromic and Nonsyndromic Obesity: Underlying Genetic Causes in Humans

Syndromic and Nonsyndromic Obesity: Underlying Genetic Causes in Humans

Genetics of Obesity in Humans: A Clinical Review

Genetics, epigenetics and transgenerational transmission of obesity in children

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