Obesity

Gnpda2 obesity in children – The current review of adolescent obesity: the role of genetic factors

Abstract Background: Recent genome wide association studies GWAS and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms SNPs associated with obesity, mostly in Europeans. Table 1 Characteristics of the study population Full size table.

However, few limitations should also be noted. Several single-gene disorders result in severe, early-onset obesity. Beutler B, Cerami A. Abstract Background. Data from the Fels longitudinal study.

  • The association of the KQ polymorphism of the plasma cell glycoprotein-1 gene with type 2 diabetes and hypertension depends on size at birth.

  • Sincegenome-wide association studies GWAS have identified adult obesity-susceptibility loci, and some of those loci are associated with childhood obesity 1 - 4.

  • Nat Rev Genet ; 10 : — Pediatrics ; : e—e

  • The obesity epidemic and its impact on hypertension.

MeSH terms

J Hum Genet ; 56 : — The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI. Hypertension ; 54 : 84— None of the hypertensive children were on antihypertensive drugs.

Genome-wide scan for loci of adolescent obesity and their relationship with blood pressure. Methods: Anthropometric indices were measured in children Each SNP was bi-allelic and was coded 0, 1, or 2 to represent the number of risk alleles carried. The sympathetic control of blood pressure.

  • Therefore, obese and non-obese type 2 diabetic patients may have distinct genetic susceptibility loci.

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  • For FTO gene, five studies suggested a significant association, 27282930 but one study revealed null association.

  • Mitchell1 Hakon Hakonarson2, 3, 4 Timothy R. Objective: Genome-wide association studies GWAS have identified some common variants associated with obesity risk in European descents.

  • Figure 1.

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96, East and South Asians. In the present study these SNPs were selected for re-analysis using quantile regression. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Mitchell1 Hakon Hakonarson2, 3, 4 Timothy R. BMC Med Genet ; 11 : Obesity Silver Spring.

Table 1. Monogenic forms of early-onset obesity Several single-gene disorders result in severe, early-onset obesity. Reprints and Permissions. These helped us obtain high quality and accurate results in the genetic study of obesity. Results 3. N Engl J Med ; : —

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Table 1 Characteristics of the study population Full size table. Clin Endocrinol Oxf Common variants near MC4R are associated with fat mass, weight and risk of obesity. Issue Date : July

Supporting Information. Genome Res 6: — For non-Gaussian gnpda2 obesity in children, the continuous variables are presented as obessity and interquartile range and analyzed by Mann-Whitney test. The anthropometric indices of body composition and adipose distribution were measured and calculated. Obesity results from excess body fat accumulation and is a major risk factor for type 2 diabetes.

Multi-ethnic studies in complex traits. Common variants recently identified by GWASs have a limited predictive value for obesity risk []. Diabetologia — Am J Epidemiol. Single-nucleotide polymorphism rs of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance. N Engl J Med —

Obesity Silver Spring Dec; 19 12 —9. Physical activity attenuates the hcildren of FTO variants on obesity risk: a meta analysis ofadults and 19, children. Publication types Research Support, Non-U. Participants included Chinese children, aged 6—18 years. Download citation. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.

Introduction

Journal of Pediatric Endocrinology and Metabolism, Vol. The SIM1 gene encodes a transcription factor essential for formation of the supraoptic and paraventricular PVN nuclei of the hypothalamus. View Article Google Scholar 3. Hum Genet. However, other SNPs were not associated with anthropometric indices of obesity in our cohort.

Gudbjartsson et al. It is true BMI curve in children is therefore genetically programmed, but at childrej same time environmental circumstances are able to modify this curve 8. Metrics details. A new highly penetrant form of obesity due to deletions on chromosome 16p Hirschhorn JN: Genomewide association studies - illuminating biologic pathways.

Chin J Evid Based Pediatr ; 5 : 4— Linear regression and genetic additive model were used to test for the association betweens SNPs and obesity-related indices weight, body mass index BMIwaist-to-height ratio and body fat. Learn More. Skip to main content Thank you for visiting nature.

In the obedity study, we aimed to examine the associations of these 11 GWAS-identified SNPs with central obesity and also to investigate the joint effect of these SNPs on central obesity among the Chinese children. Your documents are now available to view. Bouchard C. Antuna-Puente, M. Diabetes — Diabetes — Supporting Information.

MINI REVIEW article

Diabetologia — Another study that assessed the same polymorphism of MC4R gene highlighted a significant association with obesity in Mexican children PPAR Res. Obes Rev ; 9 : —

Nat Genet ; 41 : 25— In the two studies [ 9091 ], 16p Humans are usually diploid and they have two copies of each autosomal region, one per chromosome. Conceived and designed the experiments: JM XW. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Diabetes: a challenge for China in the 21st century.

Children obesity develops in response to several factors, where nutrition and energy expenditure play a determinant role [ 4 ]. The Benjamini and Hochberg adjustment was applied to value, and an adjusted value of 0. Issue Date : April Maddux BA, Goldfine ID: Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit. Nevertheless, further studies are needed to fully understand the role of the genome in childhood obesity onset.

J Biol Chem. Hah et al. High-resolution homozygosity mapping in large consanguineous pedigrees is a powerful approach to discovering new obesity loci with a recessive mode of inheritance, as recently exemplified by syndromic forms of obesity [ ].

Eur J Med Genet. The SNP rs is also associated with an increased risk of pediatric-onset type 2 diabetes in the Mexican population [ 11 ]. Skip to main content. Ashwell M, Hsieh SD. An integrative strategy for the early identification of obesity-predisposed subjects. Pediatr Neonatol. Curr Diab Rep.

  • Eur Rev Med Pharmacol Sci.

  • Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96, East and South Asians.

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  • Atherosclerosis ; : —

Xi, B. Abstract Background: Recent genome wide association studies GWAS and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms SNPs associated with obesity, mostly in Europeans. In: Quantile Regression. Hypertension ; 51 : — Timothy R. Figure 2.

Obesogenic environment is only a trigger, and not the leading-cause for excessive weight gain, a genetic susceptibility to fat gain being mandatory for an individual to become obese 5 — 7. Basic characteristics of participants in the case-control study based on WHtR criteria. View Article Google Scholar 9. Obesity-associated gene TMEM18 has a role in the central control of appetite and body weight regulation. Abstract Background.

Publication types

This pattern of association may be due to the biological limitations gnpda2 obesity in children increasing BMI greatly beyond the 95 th percentile, and so finding the strongest association at the 95 th BMI percentile would not be expected. Nat Genet. Author Contributions Study concept and design: JM. Individuals with high-risk alleles could be prescribed lifestyle modifications such as weight loss, in order to offset risk of hypertension development.

Tumor necrosis factor-alpha eliminates binding of NF-Y gnpda2 obesity in children an octamer-binding protein to cjildren lipoprotein lipase promoter in 3T3-L1 adipocytes. However, the levels of these clinical outcomes in the obesity group fall in normal ranges. In our study, the percentage of explained variance in the overall children sample was almost two-fold of that in adults 0. View Article Google Scholar 3. Endocr J. It has been reported that the genotype-phenotype association varies in diverse groups of patients, and results need to be verified in a specific population [ 9 ]. Nat Genet.

J Pediatr Endocrinol Metab. J Clin Endocrinol Metab ; 95 : — A total of patients, who had obewity diagnosed with T2DM in the Department of Endocrinology at the Second Hospital of Jilin University during the period from October to Octoberwere enrolled in the study. Cite this. The association of the KQ polymorphism of the plasma cell glycoprotein-1 gene with type 2 diabetes and hypertension depends on size at birth. Together, the studies reviewed in this section highlight the complex interplay between genetic susceptibility to obesity and the experienced environment. Yu, S.

In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. After additional adjustment for BMI, none remained statistically significant Tables 2 and 3. About gnpda2 obesity in children article Cite this article Xi, B. Measurements were taken on the right arm in sitting position with the elbow at the level of the right atrium, using an appropriately sized cuff. Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96, East and South Asians. Rebbeck1 and Struan F. This was a genotype—phenotype association study.

Introduction

A novel homozygous missense mutation of the leptin gene NK in an obese Egyptian patient. Therefore, environmental factors just favor the phenotypic expression in individuals programmed to become obese 8. Programming towards childhood obesity. Nat Genet ; 42 : —

There is evidence that early-onset obesity is a heritable disorder, and a range of genetic factors have recently been shown to cause monogenic, syndromic and polygenic forms of obesity, in some cases interacting with environmental exposures. An gnpda2 obesity between the FTO obesity risk genotype and physical activity on BMI variation or obesity risk has been consistently reported in nine independent studies including adults and adolescents [ 99— ]. The CG promoter polymorphism of the IL-6 gene affects energy expenditure and insulin sensitivity. Therefore, screening programs could be useful in identifying high-risk children, who could benefit from proper prophylactic measures. Interleukin IL 6 is a proinflammatory cytokine found to modulate the function of adipose tissue by regulating energy balance, presenting high levels in both obesity and cardiovascular diseases — The association of the N D variant with BMI and obesity was confirmed in two large adult European populations [ 6364 ].

However, few studies have focused on the association of these loci with blood pressure BP and hypertension, especially in East Asians. Moreover, FTO rs SNP was reported to be associated with higher fasting insulin, glucose, triglycerides and lower high-density lipoprotein cholesterol through the effect on BMI. Nat Genet ; 41 : 25— Received : 08 December This information may help our understanding of the association between obesity and hypertension.

Articles in the same Issue

Published : 16 April Associations of six single nucleotide polymorphisms in obesity-related genes with BMI and risk of obesity in Chinese children. External link. However, their influences on obesity-related indices for the Chinese children at puberty are not widely clear yet.

In addition, rs was associated with four indices in boys, but not in girls. Article Google Scholar. Nat Genet. This modeling approach, coupled with large sample sizes and valid environmental measures, could advance the study of childhood obesity gene-environment interactions. Nat Rev Genet.

However, their influences on obesity-related indices for the Chinese children at puberty are not widely children yet. Drafting of the manuscript: BX and XZ. Thank you for visiting nature. Liao TF, editor. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In conclusion, we found that previously identified adult obesity-susceptibility loci were more strongly associated with childhood BMI at the upper tail of the BMI distribution.

Common nonsynonymous variants in PCSK1 confer risk of obesity. None of the hypertensive children were on antihypertensive drugs. All participating children and their parents gave written informed consent under protocols provided by the Capital Institute of Paediatrics that clearly stated that blood samples would be used for scientific research purposes, including genetic studies. BMC Med Genet ; 11 : Can J Cardiol ; 28 : —

The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Importantly, these studies modeled the mean BMI, or BMI categories, and it would be of interest to determine if gene-environment interactions are uniform across the BMI distribution. Author manuscript; available in PMC Dec 1. Physical activity modifies the associations between genetic variants and hypertension in the Chinese children. A limitation of modeling the mean BMI is that the associations at the upper and lower tails of the distribution are not distinguished, and the upper tail of the BMI distribution is of primary interest when studying childhood obesity.

  • In this study, because of the restriction of available data in this ongoing project, we did not consider the factors of food intake, physical activity, sleep, family environment and other variables, which may be involved as either confounders or gene-environment interactions. Publication types Research Support, Non-U.

  • Common variants near MC4R are associated with fat mass, weight and risk of obesity.

  • A new missense mutation in the leptin gene causes mild obesity and hypogonadism without affecting T cell responsiveness.

  • Accepted 16 Apr

  • Overexpression of FTO leads to increased food intake and results in obesity. The association between deletions on chromosome 16p

Arch Pediatr Adolesc Med. Sincegenome-wide association studies GWAS have identified adult obesity-susceptibility loci, and some of those loci are associated with childhood obesity 1 - 4. Statistical analyses were performed with SPSS, version In support of this hypothesis, there is evidence that more physical activity attenuates the association between FTO and BMI in children 12 - Influence of physical inactivity on associations between single nucleotide polymorphisms and genetic predisposition to childhood obesity. Resting BP was measured in accordance with standard procedures and recommendations. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.

Arch Pediatr Adolesc Med. In addition, normotensive children from the BCAMS Study gnpda2 obesity in children informed consent for participation in the study and agreed to undergo testing on their fasting blood. Measurements were taken on the right arm in sitting position with the elbow at the level of the right atrium, using an appropriately sized cuff. BMI z-seore Chr.

Received : 08 December A genotype risk score was created by summing the number of risk alleles carried at the 8 obesity-susceptibility loci. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Diabetes ; 57 : —

Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. All analyses were performed using the simultaneous quantile regression command in Stata In contrast to linear regression and logistic regression, quantile regression allows for the study of predictors across the entire BMI distribution, without having to categorize, and may provide additional insight into the relationship between obesity-susceptibility loci and BMI 7. Cardiovascular Diabetology Individuals with high-risk alleles could be prescribed lifestyle modifications such as weight loss, in order to offset risk of hypertension development.

References 1. FTO protein is highly expressed in the hypothalamus and seems to have an important role in the energy homeostasis. Genome-wide scan for loci of adolescent obesity and their relationship with blood pressure. Copyright notice. Supplementary Table S1. Received : 08 December

  • A comparison of tests for Hardy-Weinberg equilibrium.

  • All participating children and their parents gave written informed consent under protocols provided by the Capital Institute of Paediatrics that clearly stated that blood samples would be used for scientific research purposes, including genetic studies. Revised : 15 January

  • Finally, in healthy control and in T2DM group were enrolled. Eur J Nutr.

  • Mol Genet Metab. Kang, J.

To date, five studies have investigated the association of FTO SNP with hypertension, 26272829children and only one study has examined the association of MC4R SNP with hypertension, 27 while no study has been performed to assess whether other obesity loci are associated with hypertension. Circ Cardiovasc Genet ; 2 : — National Center for Biotechnology InformationU. Nat Genet ; 41 : 18— Results Each additional increase in genotype risk score was associated with an increase in BMI z-score at the 5th, 15th, 25th, 50th, 75th, 85th and 95th BMI z-score percentiles by 0.

Association analyses of obdsity, individuals reveal 18 new loci associated with body mass index. The role of obesity-associated loci identified in genome-wide association studies in the determination children pediatric BMI. Based on the Chinese age- and sex-specific BP standards, hypertensive cases and controls with normal BP were identified. Methods: Anthropometric indices were measured in children Associations of six single nucleotide polymorphisms in obesity-related genes with BMI and risk of obesity in Chinese children. National Center for Biotechnology InformationU. Hypertension trends in Chinese children in the national surveys, to

Gene-environment interactions Environmental factors, such as diet, physical activity, age, gender, socio-economic status and ethnicity, among others, have been obesihy to modulate the risk for obesity [ 20 ]. Associations of the FTO rs and the MC4R rs polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low. Int J Endocrinol.

Individuals with cyildren alleles could be prescribed lifestyle modifications such as weight loss, in order to offset risk of hypertension development. Thank you for visiting nature. After additional adjustment for BMI, none remained significant. Nat Genet ; 40 : — A common variant of the FTO gene is associated with not only increased adiposity but also elevated blood pressure in French Canadians. Subjects Disease genetics Hypertension Obesity Paediatrics. Resting BP was measured in accordance with standard procedures and recommendations.

Obesity results from excess body fat accumulation and is a major risk factor for type 2 diabetes. SNPs, rs and rs explained children. Environmental factors, such as massive marketing campaigns for food leading to over-nutrition and snacking and the decline in physical activity, have undoubtedly contributed to the increased prevalence of overweight and obesity in children, but these cannot be considered as the only causes. Methodology 2.

Supplementary Materials. These findings suggest that GNPDA2 may be a critical gene for lipid and glucose metabolism, and the expression level of GNPDA2 alters the transcriptome profile of human adipose-derived mesenchymal stem cells. D1, pp. JK and YC revised the manuscript critically for intellectual content. BMC Med Genet.

High-resolution homozygosity mapping in large consanguineous pedigrees is a powerful approach to cihldren new obesity loci with a recessive mode of inheritance, as recently exemplified by syndromic forms of obesity [ ]. Lloyd, S. Nevertheless, the genetic susceptibility for obesity can be influenced by dietary interventions in combination with exercise, as stated by Zou et al. View at: Google Scholar S.

Supplementary information. All participating children and their parents gave written informed consent under protocols provided rates europe gndpa2 Capital Institute of Paediatrics that clearly stated that blood samples would be used for scientific research purposes, including genetic studies. SNPs, rs and rs explained 0. Association analyses ofindividuals reveal 18 new loci associated with body mass index. Quantile specific penetrance of genes affecting lipoproteins, adiposity and height. Physical activity modifies the associations between genetic variants and hypertension in the Chinese children.

Berg and P. The influences of these factors and the potential gene-environment interactions will be evaluated in the next step of this ongoing gnpd2. Leonardson and colleagues children ] found that gene-expression variations are strongly connected to clinical traits related to obesity, such as hip circumference, but depend on the nutritional state fasted or fed. Early-onset obesity is associated with an increased incidence of adult obesity [ 5 ], type 2 diabetes [ 6 ], nonalcoholic fatty liver disease [ 7 ] and cardiovascular risk factors [ 8 ].

The roles of these genes are complex and interdependent, being linked to different gpnda2 in obesity development, such as appetite behavior, control of food intake and energy balance, insulin signaling, lipid and glucose metabolism, metabolic disorders, adipocyte differentiation, and so on. The genotypes of these seven loci in healthy controls and type 2 diabetic patients with overweight and obesity are shown in Table 4. On the contrary, the TMEM18 gene has a significant effect in boys but not girls.

Increased length of stay and hospital charges in adolescents with type 1 diabetes and psychiatric illness. Sato, and K. This leptin resistance mechanism was related to the presence of the A allele variant of the FTO gene 36partially explaining the associations of the FTO gene polymorphisms with increased dietary consumption 37 or a hyperphagic phenotype 27 In the past few years, the work of genome-wide association studies GWAS has produced a number of novel obesity genes. Int J Obes Lond ; 32 : — Skip to main content. Obesity susceptibility genetic variants identified from recent genome-wide association studies: implications in a chinese population.

Int J Cardiol Nat Rev Neurosci ; 7 : — Guyenet PG. As obesity is strongly associated with hypertension, the two diseases may share the similar genetic architecture. Revised : 15 January

International Journal of Endocrinology

BMI z-seore Chr. Arch Pediatr Adolesc Med. Advanced search.

Diabetes — Mol Nutr Food Res — Obesity is partially due to environmental factors and lifestyle choices, but is also attributed to genetic susceptibility. Influence of physical inactivity on associations between single nucleotide polymorphisms and genetic predisposition to childhood obesity. The best illustration is certainly the case of a child with congenital leptin deficiency who was treated with subcutaneous injections of recombinant human leptin, leading to the correction of all the phenotypic abnormalities seen in this patient [ 37 ]. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

  • About this article. Mutat Res.

  • You have full access to this article via your institution. Atherosclerosis ; : —

  • J Clin Endocrinol Metab. TMEM18 was associated with obesity among boys but not among girls.

  • Mol Psychiatry —

  • BMI's were converted to age and gender specific z-scores 9. In that study each additional risk allele carried was associated with increases in BMI, and the associations were stronger at the upper tail, compared to the lower tail, of the BMI distribution 8.

Participants included Chinese children, aged 6—18 years. Additional information Children Information accompanies this paper on International Journal of Obesity website. Resting BP was measured in accordance with standard procedures and recommendations. A genotype risk score was created by summing the number of risk alleles carried at the 8 obesity-susceptibility loci. In contrast, rs showed a strong association only in girls.

BMC Med Genet. The primers used children this study are listed in Supplementary Table 1. Another well-documented fact is that fetal and early postnatal environmental events, such as maternal nutritional status during pregnancy, obeeity smoking, gestational diabetes, increased birth weight, rapid weight gain, or feeding practices, may also influence the development of obesity later in life 8 — Obesity — A study including Finnish men demonstrated that CDKAL1 rs was associated with increased risk for type 2 diabetes, likely via impairing insulin secretion [ 34 ]. Eur J Clin Nutr. Authors' contributions Both authors contributed to the conception and production of the manuscript and approved the final version.

Journal and Issue

Table 1 PCR primers Full size table. Pharmacology — Pritchard, and P.

An exclusion criterion was related to children with foreign parents and grandparents. An interaction between the FTO obesity risk genotype and physical activity on BMI variation or obesity risk has been consistently reported in nine independent studies including adults and adolescents [ 99— ]. Popul Health Metrics. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Received : 29 July A survey of genetic human cortical gene expression.

SBP was determined by obeaity onset of the first Korotkoff sound K1 and DBP was determined by the fourth Korotkoff sound K4 it should be noted that as the fifth Korotkoff sound K5 is recommended by the National Heart, Lung and Blood Institute, 20 our measurement of DBP using K4 should be interpreted with caution, although childhood K4 seems be superior to K5 in predicting hypertension in adulthood Learn More. Skip to main content Thank you for visiting nature. None of the hypertensive children were on antihypertensive drugs.

Background

The fat-mass and obesity-associated FTO gene, physical gnpda2 obesity in children, and risk of incident cardiovascular events in white women. Mol Nutr Food Res ; 55 : — In contrast to linear regression and logistic regression, quantile regression allows for the study of predictors across the entire BMI distribution, without having to categorize, and may provide additional insight into the relationship between obesity-susceptibility loci and BMI 7. The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI. Publication types Research Support, Non-U.

This polymorphism has also been associated with BMI in Mexican children [ 28 ]. Karanian, O. Am J Clin Nutr — The association of the N D variant with BMI and obesity was confirmed in two large adult European populations [ 6364 ]. It is true BMI curve in children is therefore genetically programmed, but at the same time environmental circumstances are able to modify this curve 8.

In contrast, gnpva2 showed a strong association only in girls. Gnpda2 obesity in children you for visiting nature. Author Contributions Study concept and design: JM. Dietary energy density affects fat mass in early adolescence and is not modified by FTO variants. Footnotes Disclosure No conflicts of interest to declare. In that study each additional risk allele carried was associated with increases in BMI, and the associations were stronger at the upper tail, compared to the lower tail, of the BMI distribution 8.

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