TY - GEN A1 - Volckmar, Anna-Lena A1 - Han, Chung-Ting A1 - Pütter, Carolin A1 - Haas, Stefan A1 - Vogel, Carla I. G. A1 - Knoll, Nadja A1 - Struve, Christoph A1 - Göbel, Maria A1 - Haas, Katharina A1 - Herrfurth, Nikolas A1 - Jarick, Ivonne A1 - Grallert, Harald A1 - Schürmann, Annette A1 - Al- Hasani, Hadi A1 - Hebebrand, Johannes A1 - Sauer, Sascha A1 - Hinney, Anke T1 - Analysis of genes involved in body weight regulation by targeted re-sequencing T2 - PLoS ONE N2 - Introduction Genes involved in body weight regulation that were previously investigated in genome-wide association studies (GWAS) and in animal models were target-enriched followed by massive parallel next generation sequencing. Methods We enriched and re-sequenced continuous genomic regions comprising FTO, MC4R, TMEM18, SDCCAG8, TKNS, MSRA and TBC1D1 in a screening sample of 196 extremely obese children and adolescents with age and sex specific body mass index (BMI) >= 99th percentile and 176 lean adults (BMI <= 15th percentile). 22 variants were confirmed by Sanger sequencing. Genotyping was performed in up to 705 independent obesity trios (extremely obese child and both parents), 243 extremely obese cases and 261 lean adults. Results and Conclusion We detected 20 different non-synonymous variants, one frame shift and one nonsense mutation in the 7 continuous genomic regions in study groups of different weight extremes. For SNP Arg695Cys (rs58983546) in TBC1D1 we detected nominal association with obesity (p(TDT) = 0.03 in 705 trios). Eleven of the variants were rare, thus were only detected heterozygously in up to ten individual(s) of the complete screening sample of 372 individuals. Two of them (in FTO and MSRA) were found in lean individuals, nine in extremely obese. In silico analyses of the 11 variants did not reveal functional implications for the mutations. Concordant with our hypothesis we detected a rare variant that potentially leads to loss of FTO function in a lean individual. For TBC1D1, in contrary to our hypothesis, the loss of function variant (Arg443Stop) was found in an obese individual. Functional in vitro studies are warranted. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 423 KW - melanocortin-4 receptor gene KW - stimulated glucose-uptake KW - life-style intervention KW - onset extreme obesity KW - genome-wide analysis KW - mass index KW - FTO gene KW - fat mass KW - overweight children KW - diabetes-melllitus Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-410289 ER - TY - GEN A1 - Müller, Steffen A1 - Carlsohn, Anja A1 - Müller, Juliane A1 - Baur, Heiner A1 - Mayer, Frank T1 - Influence of Obesity on Foot Loading Characteristics in Gait for Children Aged 1 to 12 Years N2 - Background Overweight and obesity are increasing health problems that are not restricted to adults only. Childhood obesity is associated with metabolic, psychological and musculoskeletal comorbidities. However, knowledge about the effect of obesity on the foot function across maturation is lacking. Decreased foot function with disproportional loading characteristics is expected for obese children. The aim of this study was to examine foot loading characteristics during gait of normal-weight, overweight and obese children aged 1-12 years. Methods A total of 10382 children aged one to twelve years were enrolled in the study. Finally, 7575 children (m/f: n = 3630/3945; 7.0 +/- 2.9yr; 1.23 +/- 0.19m; 26.6 +/- 10.6kg; BMI: 17.1 +/- 2.4kg/m(2)) were included for (complete case) data analysis. Children were categorized to normalweight (>= 3rd and <90th percentile; n = 6458), overweight (>= 90rd and <97th percentile; n = 746) or obese (>97th percentile; n = 371) according to the German reference system that is based on age and gender-specific body mass indices (BMI). Plantar pressure measurements were assessed during gait on an instrumented walkway. Contact area, arch index (AI), peak pressure (PP) and force time integral (FTI) were calculated for the total, fore-, mid-and hindfoot. Data was analyzed descriptively (mean +/- SD) followed by ANOVA/Welch-test (according to homogeneity of variances: yes/no) for group differences according to BMI categorization (normal-weight, overweight, obesity) and for each age group 1 to 12yrs (post-hoc Tukey Kramer/Dunnett's C; alpha = 0.05). Results Mean walking velocity was 0.95 +/- 0.25 m/s with no differences between normal-weight, overweight or obese children (p = 0.0841). Results show higher foot contact area, arch index, peak pressure and force time integral in overweight and obese children (p< 0.001). Obese children showed the 1.48-fold (1 year-old) to 3.49-fold (10 year-old) midfoot loading (FTI) compared to normal-weight. Conclusion Additional body mass leads to higher overall load, with disproportional impact on the midfoot area and longitudinal foot arch showing characteristic foot loading patterns. Already the feet of one and two year old children are significantly affected. Childhood overweight and obesity is not compensated by the musculoskeletal system. To avoid excessive foot loading with potential risk of discomfort or pain in childhood, prevention strategies should be developed and validated for children with a high body mass index and functional changes in the midfoot area. The presented plantar pressure values could additionally serve as reference data to identify suspicious foot loading patterns in children. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 284 KW - plantar pressure distribution KW - body-mass index KW - prepubescent children KW - overweight children KW - childhood obesity KW - walking KW - speed KW - forces KW - adolescents KW - prevalence Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-90108 ER - TY - JOUR A1 - Müller, Steffen A1 - Carlsohn, Anja A1 - Müller, Juliane A1 - Baur, Heiner A1 - Mayer, Frank T1 - Influence of Obesity on Foot Loading Characteristics in Gait for Children Aged 1 to 12 Years JF - PLoS one N2 - Background Overweight and obesity are increasing health problems that are not restricted to adults only. Childhood obesity is associated with metabolic, psychological and musculoskeletal comorbidities. However, knowledge about the effect of obesity on the foot function across maturation is lacking. Decreased foot function with disproportional loading characteristics is expected for obese children. The aim of this study was to examine foot loading characteristics during gait of normal-weight, overweight and obese children aged 1-12 years. Methods A total of 10382 children aged one to twelve years were enrolled in the study. Finally, 7575 children (m/f: n = 3630/3945; 7.0 +/- 2.9yr; 1.23 +/- 0.19m; 26.6 +/- 10.6kg; BMI: 17.1 +/- 2.4kg/m(2)) were included for (complete case) data analysis. Children were categorized to normalweight (>= 3rd and <90th percentile; n = 6458), overweight (>= 90rd and <97th percentile; n = 746) or obese (>97th percentile; n = 371) according to the German reference system that is based on age and gender-specific body mass indices (BMI). Plantar pressure measurements were assessed during gait on an instrumented walkway. Contact area, arch index (AI), peak pressure (PP) and force time integral (FTI) were calculated for the total, fore-, mid-and hindfoot. Data was analyzed descriptively (mean +/- SD) followed by ANOVA/Welch-test (according to homogeneity of variances: yes/no) for group differences according to BMI categorization (normal-weight, overweight, obesity) and for each age group 1 to 12yrs (post-hoc Tukey Kramer/Dunnett's C; alpha = 0.05). Results Mean walking velocity was 0.95 +/- 0.25 m/s with no differences between normal-weight, overweight or obese children (p = 0.0841). Results show higher foot contact area, arch index, peak pressure and force time integral in overweight and obese children (p< 0.001). Obese children showed the 1.48-fold (1 year-old) to 3.49-fold (10 year-old) midfoot loading (FTI) compared to normal-weight. Conclusion Additional body mass leads to higher overall load, with disproportional impact on the midfoot area and longitudinal foot arch showing characteristic foot loading patterns. Already the feet of one and two year old children are significantly affected. Childhood overweight and obesity is not compensated by the musculoskeletal system. To avoid excessive foot loading with potential risk of discomfort or pain in childhood, prevention strategies should be developed and validated for children with a high body mass index and functional changes in the midfoot area. The presented plantar pressure values could additionally serve as reference data to identify suspicious foot loading patterns in children. KW - plantar pressure distribution KW - body-mass index KW - prepubescent children KW - overweight children KW - childhood obesity KW - walking KW - speed KW - forces KW - adolescents KW - prevalence Y1 - 2016 U6 - https://doi.org/10.1371/journal.pone.0149924 SN - 1932-6203 VL - 11 IS - 2 PB - Public Library of Science CY - Lawrence, Kan. ER -