No abstract

No abstract

IMPORTANCE Genome-wide association studies have identified genetic loci influencing obesity risk in children. However, the importance of these loci in the associations with weight reduction through lifestyle interventions has not been investigated in large intervention trials.OBJECTIVE To evaluate the associations between various obesity susceptibility loci and changes in body weight in children during an in-hospital, lifestyle intervention program.DESIGN, SETTING, AND PARTICIPANTS Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children (LOGIC), an interventional prospective cohort study, enrolled 1429 children with overweight or obesity to participate in an in-hospital lifestyle intervention program. Genotyping of 56 validated obesity single-nucleotide variants (SNVs) was performed, and the associations between the SNVs and body weight reduction during the intervention were evaluated using linear mixed-effects models for each SNV.

Context: Genome-wide association studies have shown that the melatonin receptor 1B (MTNR1B) gene locus is strongly associated with fasting glucose and b-cell function. However, data are rather limited to the adult population and normal-weight children. So far, little is known whether similar associations are present in overweight and obese children and adolescents. Objective: The aim is to investigate an MTNR1B polymorphism in a sample of 310 overweight and obese children and adolescents (mean body mass index standard deviation score (BMI-SDS)): 2.74 (G0.55), mean age: 14 (G2) years), who participated in a short-term weight-loss program based on energy reduction, physical activity, and behavior therapy. Methods: We investigated an association between genotype and fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and of b-cell function (HOMA-B), and anthropometric parameters and their change during intervention. Results: The minor G allele of polymorphism rs10830963 was significantly associated with increased fasting glucose (0.205 mmol/l, P!0.0001) and decreased HOMA-B (K0.353, P!0.0001). Categorizing the sample into BMI-SDS groups, these significant associations were abolished in children with BMI-SDS below 2.5 but remained in those with higher BMI-SDS values with stronger b-estimates. The P value for the genotype!BMI-SDS category interaction was 0.012 for fasting glucose and 0.083 for HOMA-B. There was no significant association between genotype and anthropometric parameters and their change during intervention. Conclusions: This is the first single study, replicating the association between the MTNR1B locus and diabetes-related traits in overweight and obese children and adolescents. The effect sizes in children and adolescents seem to be stronger than in adults and differed among BMI-SDS categories.

BackgroundRecent publications have reported contradictory data regarding mitochondrial DNA (mtDNA) variation and its association with body mass index. The aim of the present study was to compare the frequencies of mtDNA haplogroups as well as control region (CR) polymorphisms of obese juveniles (n = 248) and obese adults (n = 1003) versus normal weight controls (njuvenile = 266, nadults = 595) in a well-defined, ethnically homogenous, age-matched comparative cohort of Austrian Caucasians.Methodology and Principal FindingsUsing SNP analysis and DNA sequencing, we identified the nine major European mitochondrial haplogroups and CR polymorphisms. Of these, only the T haplogroup frequency was increased in the juvenile obese cohort versus the control subjects [11.7% in obese vs. 6.4% in controls], although statistical significance was lost after adjustment for sex and age. Similar data were observed in a local adult cohort, in which haplogroup T was found at a significantly higher frequency in the overweight and obese subjects than in the normal weight group [9.7% vs. 6.2%, p = 0.012, adjusted for sex and age]. When all obese subjects were considered together, the difference in the frequency of haplogroup T was even more clearly seen [10.1% vs. 6.3%, p = 0.002, OR (95% CI) 1.71 (1.2–2.4), adjusted for sex and age]. The frequencies of the T haplogroup-linked CR polymorphisms C16294T and the C16296T were found to be elevated in both the juvenile and the adult obese cohort compared to the controls. Nevertheless, no mtDNA haplogroup or CR polymorphism was robustly associated with any of several investigated metabolic and cardiovascular parameters (e.g., blood pressure, blood glucose concentration, triglycerides, cholesterol) in all obese subjects.Conclusions and SignificanceBy investigation of this large ethnically and geographically homogenous cohort of Middle European Caucasians, only mtDNA haplogroup T was identified as an obesity risk factor.