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Differences in fat and muscle mass associated with a functional human polymorphism in a post-transcriptional BMP2 gene regulatory element.

ABSTRACT: A classic morphogen, bone morphogenetic protein 2 (BMP2) regulates the differentiation of pluripotent mesenchymal cells. High BMP2 levels promote osteogenesis or chondrogenesis and low levels promote adipogenesis. BMP2 inhibits myogenesis. Thus, BMP2 synthesis is tightly controlled. Several hundred nucleotides within the 3' untranslated regions of BMP2 genes are conserved from mammals to fishes indicating that the region is under stringent selective pressure. Our analyses indicate that this region controls BMP2 synthesis by post-transcriptional mechanisms. A common A to C single nucleotide polymorphism (SNP) in the BMP2 gene (rs15705, +A1123C) disrupts a putative post-transcriptional regulatory motif within the human ultra-conserved sequence. In vitro studies indicate that RNAs bearing the A or C alleles have different protein binding characteristics in extracts from mesenchymal cells. Reporter genes with the C allele of the ultra-conserved sequence were differentially expressed in mesenchymal cells. Finally, we analyzed MRI data from the upper arm of 517 healthy individuals aged 18-41 years. Individuals with the C/C genotype were associated with lower baseline subcutaneous fat volumes (P = 0.0030) and an increased gain in skeletal muscle volume (P = 0.0060) following resistance training in a cohort of young males. The rs15705 SNP explained 2-4% of inter-individual variability in the measured parameters. The rs15705 variant is one of the first genetic markers that may be exploited to facilitate early diagnosis, treatment, and/or prevention of diseases associated with poor fitness. Furthermore, understanding the mechanisms by which regulatory polymorphisms influence BMP2 synthesis will reveal novel pharmaceutical targets for these disabling conditions.

SUBMITTER: Devaney JM

PROVIDER: S-EPMC4147943 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Differences in fat and muscle mass associated with a functional human polymorphism in a post-transcriptional BMP2 gene regulatory element.

Devaney Joseph M JM Tosi Laura L LL Fritz David T DT Gordish-Dressman Heather A HA Jiang Shan S Orkunoglu-Suer Funda E FE Gordon Andrew H AH Harmon Brennan T BT Thompson Paul D PD Clarkson Priscilla M PM Angelopoulos Theodore J TJ Gordon Paul M PM Moyna Niall M NM Pescatello Linda S LS Visich Paul S PS Zoeller Robert F RF Brandoli Cinzia C Hoffman Eric P EP Rogers Melissa B MB

Journal of cellular biochemistry 20090801 6

A classic morphogen, bone morphogenetic protein 2 (BMP2) regulates the differentiation of pluripotent mesenchymal cells. High BMP2 levels promote osteogenesis or chondrogenesis and low levels promote adipogenesis. BMP2 inhibits myogenesis. Thus, BMP2 synthesis is tightly controlled. Several hundred nucleotides within the 3' untranslated regions of BMP2 genes are conserved from mammals to fishes indicating that the region is under stringent selective pressure. Our analyses indicate that this regi ...[more]

PMID: 19492344

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Project description:A single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is a strong predictor of obesity in humans. The FTO SNP (rs1421085) results in a T to C nucleotide substitution that may result in an increased risk for obesity in individuals who carry at least one C allele. The purpose of this investigation was to characterize the FTO genotype in a cohort of exercise-trained men and women.We tested 108 exercise-trained individuals that included professional mixed martial arts fighters, competitive distance runners, collegiate swimmers, stand-up paddlers as well as a cohort of recreational bodybuilders. Body composition was assessed via dual-energy x-ray absorptiometry (DXA). Saliva samples were collected in order to genotype participants and quantify cortisol levels.The physical characteristics of the subjects were as follows (mean±SD): body weight 74.5±15.6 kg; height 171.5±9.5 cm; bone mineral content 2.8±0.7 kg; fat mass 15.7±5.5 kg; lean body mass 55.9±14.4 kg; % body fat 21.6±7.0. Independent samples t tests showed that C allele carriers (n =?54) had significantly higher fat mass t(106)?=?3.13, p <?0.01 and body fat percentage t(106)?=?2.68, p?<?0.01, relative to the TT group (n?=?54) (i.e., fat mass: C/-?17.3 ±5.6 kg, TT 14.2±4.6 kg; body fat percentage: C/- group 23.4±7.4%, TT group 19.9±6.2). No other measures of body composition were associated with the FTO genotype (i.e., body mineral density, bone mineral content, or lean body mass). Moreover, cortisol levels were significantly higher in the TT group relative to the C allele carriers t(106)?=?2.37, p =?0.02 (i.e., TT 0.35 ±0.35 ?g/dL, C/-?0.22±0.16 ?g/dL).Our findings demonstrate a relationship between C allele carriers on the FTO gene and a predisposition to a higher fat mass and body fat percentage. In addition, we found no relationship between cortisol and fat mass. However, due to the cross-sectional nature of this investigation, we cannot infer causality regarding the FTO gene and body composition.

Dataset Information

Differences in fat and muscle mass associated with a functional human polymorphism in a post-transcriptional BMP2 gene regulatory element.

Publications

Differences in fat and muscle mass associated with a functional human polymorphism in a post-transcriptional BMP2 gene regulatory element.

Similar Datasets

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