Heritability of free and receptor-bound leptin in normal twins

Jordan, Jens; Brabant, Georg; Brinsuk, Marina; Tank, Jens; Horn, Rüdiger; Luft, Friedrich C.; Busjahn, Andreas

doi:10.1152/ajpregu.00446.2004

Cited by 18 publications

(15 citation statements)

References 22 publications

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“…Although tracking per se appears not to have been demonstrated previously, Jordan et al [27] showed that circulating SLR concentrations, and leptin concentrations, bound or free, exhibited adjusted heritability estimates of 0.28 for free leptin, 0.73 for bound leptin, and 0.55 for SLR, in 24 monozygotic and 22 dizygotic twin pairs, suggesting an intrinsic genetic influence, which could be compatible with tracking. In comObes Facts 2011;4:461- 468 Tracking of Leptin and Its Soluble Receptor 467 in regain.…”

Section: Discussionmentioning

confidence: 88%

Tracking of Leptin, Soluble Leptin Receptor, and the Free Leptin Index during Weight Loss and Regain in Children

Holm¹,

Gamborg²,

Ward³

et al. 2011

Obes Facts

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Objective: To investigate changes in leptin and soluble leptin receptor (SLR) concentrations, and in the free leptin index (FLI) during weight loss and subsequent weight regain; and to ascertain whether these indices remain stable in the rank of the distribution in repeated measures (tracking) during perturbations of weight in obese children. Design and Measurements: In a longitudinal study, 115 obese children were examined during a 12- week weight loss programme and 28 months of follow-up. Height, weight, body composition, Tanner stages, testicular size, time of menarche, and concentrations of leptin and SLR were measured at baseline, on days 14, 33, and 82, and from months 10, 16, and 28. Results: During weight loss, leptin decreased and the SLR increased. During weight regain, leptin increased and the SLR decreased. The partial correlation coefficients expressing the relationship between leptin and SLR were significant in girls during both weight loss and weight regain, whereas in boys they were much weaker and not significant. Leptin, SLR and FLI exhibited individual-specific levels (tracking) during weight loss and regain in boys and girls. The observed tracking seemed stronger during weight loss than during weight regain. The observed tracking was independent of both baseline body mass index (BMI) standard deviation score (SDS) and pubertal development at baseline and of subsequent changes in BMI SDS and puberty stages. Conclusion: Leptin and the SLR exhibit tracking during weight loss and regain, which indicates individual stability in the leptin system despite challenges of weight.

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Section: Discussionmentioning

confidence: 88%

Tracking of Leptin, Soluble Leptin Receptor, and the Free Leptin Index during Weight Loss and Regain in Children

Holm¹,

Gamborg²,

Ward³

et al. 2011

Obes Facts

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“…Heritability for leptin and BMI traits has been reported previously, with evidence of shared genetic determination. 47,48 …”

Section: Discussionmentioning

confidence: 99%

Genetic Variation Within a Metabolic Motif in the Chromogranin A Promoter: Pleiotropic Influence on Cardiometabolic Risk Traits in Twins

Rao

Chiron

Wei

et al. 2012

American Journal of Hypertension

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BACKGROUND The cardiometabolic syndrome comprised of multiple correlated traits, but its origin is incompletely understood. Chromogranin A (CHGA) is required for formation of the catecholamine secretory pathway in sympathochromaffin cells. In twin pair studies, we found that CHGA traits aggregated with body mass index (BMI), as well as its biochemical determinant leptin. METHODS Here we used the twin method to probe the role of heredity in generating such risk traits, and then investigated the role of risk-trait-associated CHGA promoter genetic variation in transfected chromaffin cells. Trait heritability (h2) and shared genetic determination among traits (pleiotropy, genetic covariance, ρG) were estimated by variance components in twin pairs. RESULTS CHGA, BMI, and leptin each displayed substantial h2, and the traits also aggregated with several features of the metabolic syndrome (e.g., insulin resistance, blood pressure (BP), hypertension, catecholamines, and C-reactive protein (CRP)). Twin studies demonstrated genetic covariance (pleiotropy, ρG) for CHGA, BMI, and leptin with other metabolic traits (insulin resistance, BP, and CRP). We therefore investigated the CHGA locus for mechanisms of codetermination with such metabolic traits. A common functional variant in the human CHGA promoter (G-462A, rs9658634, minor allele frequency ~21%) was associated with leptin and CRP secretion, as well as BMI, especially in women; marker-on-trait effects on BMI were replicated across twin populations on two continents. In CHGA promoter/luciferase reporter plasmids transfected into chromaffin cells, G-462A alleles differed markedly in reporter expression. The G-462A variant disrupted predicted transcriptional control by a PPARγ/RXRα motif and costimulation by PPARγ/RXRα and their cognate ligands, differentially activated the two alleles. During chromatin immunoprecipitation, endogenous PPARγ bound the motif. CONCLUSIONS Multiple features of the metabolic syndrome are thus under joint (pleiotropic) genetic determination, with CHGA as one such contributory locus: a common polymorphism in the promoter (G-462A) of CHGA predicts such heritable metabolic traits as BMI and leptin. CHGA promoter variant G-462A was not only associated with such metabolic traits but also disrupted a PPARγ/RXRα motif and responded differentially to characteristic trans-activators of that motif. The results suggest novel links between the catecholaminergic system and risk for the metabolic syndrome as well as systemic hypertension.

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“…We hypothesize that the different prognostic effects of body fat accumulation markers imply differences in etiology, including genetic predisposition. This is supported by analysis of obesity phenotypes in twin studies, which show a genetic correlation of less than one that indicates only partly overlap between the genes determining these phenotypes [28,29]. In some of our previous studies, we did include analyses of waist and/or waist-to-hip ratios in relation to some gene variants, but the quantitative feature throughout the population range was not used in the analyses.…”

Section: Selection and Genotyping Of Variantsmentioning

confidence: 95%

Genotype-Phenotype Associations in Obesity Dependent on Definition of the Obesity Phenotype

Kring¹,

Larsen²,

Holst³

et al. 2008

Obes Facts

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Objective: In previous studies of associations of variants in the genes UCP2, UCP3, PPARG2, CART, GRL, MC4R, MKKS, SHP, GHRL, and MCHR1 with obesity, we have used a case-control approach with cases defined by a threshold for BMI. In the present study, we assess the association of seven abdominal, peripheral, and overall obesity phenotypes, which were analyzed quantitatively, and thirteen candidate gene polymorphisms in these ten genes in the same cohort. Methods: Obese Caucasian men (n = 234, BMI ≧31.0 kg/m²) and a randomly sampled non-obese group (n = 323), originally identified at the draft board examinations, were re-examined at median ages of 47.0 or 49.0 years by anthropometry and DEXA scanning. Obesity phenotypes included BMI, fat body mass index, waist circumference, waist for given BMI, intra-abdominal adipose tissue, hip circumference and lower body fat mass (%). Using logistic regression models, we estimated the odds for defined genotypes (dominant or recessive genetic transmission) in relation to z-scores of the phenotypes. Results: The minor (rare) allele for SHP 512G>C (rs6659176) was associated with increased hip circumference. The minor allele for UCP2 Ins45bp was associated with increased BMI, increased abdominal obesity, and increased hip circumference. The minor allele for UCP2 –866G>A (rs6593669) was associated with borderline increased fat body mass index. The minor allele for MCHR1 100213G>A (rs133072) was associated with reduced abdominal obesity. None of the other genotype-phenotype combinations showed appreciable associations. Conclusion: If replicated in independent studies with focus on the specific phenotypes, our explorative studies suggest significant associations between some candidate gene polymorphisms and distinct obesity phenotypes, predicting beneficial and detrimental effects, depending on compartments for body fat accumulation.

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Heritability of free and receptor-bound leptin in normal twins

Cited by 18 publications

References 22 publications

Tracking of Leptin, Soluble Leptin Receptor, and the Free Leptin Index during Weight Loss and Regain in Children

Tracking of Leptin, Soluble Leptin Receptor, and the Free Leptin Index during Weight Loss and Regain in Children

Genetic Variation Within a Metabolic Motif in the Chromogranin A Promoter: Pleiotropic Influence on Cardiometabolic Risk Traits in Twins

Genotype-Phenotype Associations in Obesity Dependent on Definition of the Obesity Phenotype

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