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Objective:To estimate the frequency of Arg64 allele of the β3-adrenergic receptor (3-BAR) gene in healthy (H) and obese (O) Hungarian children, and to look for possible associations between this polymorphism and some clinical and metabolic characteristics of obese children.Patients/methods:In all, 147 healthy (male: 68) and 295 obese (male: 168) children were examined. The average age of the children in the two groups was 12.4±1.7 vs 12.6±3.2, respectively. Exon 1 of 3-BAR was amplified by polymerase chain reaction and the fragments were digested with BstN1. In obese children, oral glucose tolerance test was carried out and blood pressure (BP) was checked.Results:The frequency of Trp64Arg polymorphism in normal and obese Hungarian children was similar (H vs O: n=14/9.5% vs n=35/11.8%). Obese children carrying the Arg64 allele (n=35, male: 23) were compared to randomly chosen, obese children without the Arg64 allele (n=35, male: 20). A significant difference was found between the body weight (81.2±23.2 vs 75.6±17.7 kg; mean±s.d.; P<0.01), body fat (38.8±3.9 vs 36.5±2.3%; mean±s.d.; P<0.05), mean fasting insulin levels (31.4±16.7 vs 16.9±7.6 μIU/ml; P<0.001) and mean systolic BP values (125.2±10.1 vs 114.5±8.3 mmHg; P<0.001) of the two obese groups.Conclusions:The frequency of Trp64Arg polymorphism was similar in Hungary as compared to other European countries. Although the prevalence of this polymorphism was similar in H and O children, the presence of Arg64 allele seems to be associated with increased adiposity, elevated systolic BP and higher fasting insulin levels.European Journal of Clinical Nutrition (2005) 59, 955–959. doi:10.1038/sj.ejcn.1602164; published online 8 June 2005 [ABSTRACT FROM AUTHOR]

Low birthweight has been epidemiologically associated with unfavourable plasma lipid profiles and enhanced risk of cardiovascular morbidity in adulthood. Plasma lipids, lipoprotein cholesterols, apolipoproteins, fatty acid composition of plasma phospholipids and basic indices of glycaemia were investigated in 10-y-old children born with similarly low birthweights as small-for-gestational-age (SGA; n= 16) or preterm infants (n= 16). Plasma total cholesterol (4.32 ± 0.57 vs 4.60 ± 0.52, mmol l[sup -1] , mean ± SD, SGA vs preterm subjects), low-density lipoprotein cholesterol (2.54 ± 0.51 vs 2. 65 ± 0.51) and high-density lipoprotein cholesterol (1.61 ± 0.25 vs 1.76 ± 0.18) concentrations did not differ between the 2 groups. There was no difference in plasma triacylglycerol, apolipoprotein A-I and B, insulin and glucose concentrations or phospholipid fatty acid values. There was no correlation between indices of lipid and carbohydrate metabolism. In conclusion, plasma lipid profiles and basic indices of glycaemia are not different in 10-y-old children born with similarly low birthweights as SGA or preterm infants. [ABSTRACT FROM AUTHOR]

Ghrelin, a regulator of food intake and energy expenditure, has been shown to be associated with insufficient sleep. The goal of the present study was to investigate the effect of a single night of total sleep deprivation on fasting saliva ghrelin and on nocturnal variation of saliva ghrelin concentration. A further aim of the study was to investigate the influence of body mass index on changes in saliva ghrelin levels. Altogether 35 adolescents (18 boys; age: 13.8 ± 1.14 years) were studied on two subsequent days (sleep and total sleep deprivation). Saliva samples were collected during the two experimental nights at 21:00 hours, 01:00 hours and 06:00 hours. Total-ghrelin concentration showed a continuous increase from the evening until 06:00 hours. This increase was blunted significantly (p = 0.003) by total sleep deprivation. Total-ghrelin level was significantly lower (p = 0.02) during total sleep deprivation at 06:00 hours (median 403.6 pg ml -1 ; 95% confidence interval: 343.1-468.9 pg ml -1 ) as compared with values during the sleep condition (median 471.2 pg ml -1 ; 95% confidence interval: 205.4-1578.7 pg ml -1 ). Acyl-ghrelin levels did not present any change at the three time points, and were not affected by total sleep deprivation. Stratifying the study population according to body mass index (normal weight and overweight/obese groups), the blunting effect of total sleep deprivation was more pronounced in the obese/overweight group (sleep: median 428.2 pg ml -1 ; 95% confidence interval: 331.3-606.9 pg ml -1 versus total sleep deprivation: median 333.1 pg ml -1 ; 95% confidence interval: 261.5-412.9 pg ml -1 ; p = 0.0479). Saliva total-ghrelin concentrations gradually increased during the night, and total sleep deprivation significantly blunted this increase. This blunting effect was mainly observed in subjects with overweight/obesity. The physiological and clinical implications of the present observation are to be clarified by further studies., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Prader-Willi syndrome (PWS) is a complex genetic disorder which involves the endocrine and neurologic systems, metabolism, and behavior. The aim of this paper is to summarize current knowledge on dietary management and treatment of PWS and, in particular, to prevent excessive weight gain. Growth hormone (GH) therapy is the recommended standard treatment for PWS children, because it improves body composition (by changing the proportion of body fat and lean body mass specifically by increasing muscle mass and energy expenditure), linear growth, and in infants, it promotes psychomotor and IQ development. In early childhood, the predominant symptom is hyperphagia which can lead to early onset, severe obesity with different obesity-related comorbidities. There are several studies on anti-obesity medications (metformin, topiramate, liraglutide, setmelanotide). However, these are still limited, and no widely accepted consensus guideline exists concerning these drugs in children with PWS. Until there is a specific treatment for hyperphagia and weight gain, weight must be controlled with the help of diet and exercise. Below the age of one year, children with PWS have no desire to eat and will often fail to thrive, despite adequate calories. After the age of two years, weight begins to increase without a change in calorie intake. Appetite increases later, gradually, and becomes insatiable. Managing the progression of different nutritional phases (0-4) is really important and can delay the early onset of severe obesity. Multidisciplinary approaches are crucial in the diagnosis and lifelong follow-up, which will determine the quality of life of these patients.

Obesity is the result of interactions between genes and environmental factors. Since monogenic etiology is only known in some obesity-related genes, a genetic risk score (GRS) could be useful to determine the genetic predisposition to obesity. Therefore, the aim of our study was to build a GRS able to predict genetic predisposition to overweight and obesity in European adolescents. A total of 1069 adolescents (51.3% female), aged 11-19 years participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were genotyped. The sample was divided in non-overweight (non-OW) and overweight/obesity (OW/OB). From 611 single nucleotide polymorphisms (SNP) available, a first screening of 104 SNPs univariately associated with obesity (p < 0.20) was established selecting 21 significant SNPs (p < 0.05) in the multivariate model. Unweighted GRS (uGRS) was calculated by summing the number of risk alleles and weighted GRS (wGRS) by multiplying the risk alleles to each estimated coefficient. The area under curve (AUC) was calculated in uGRS (0.723) and wGRS (0.734) using tenfold internal cross-validation. Both uGRS and wGRS were significantly associated with body mass index (BMI) (p < .001). Both GRSs could potentially be considered as useful genetic tools to evaluate individual's predisposition to overweight/obesity in European adolescents.

Obesity and metabolic syndrome (MetS) are worldwide major health challenges. The Mediterranean diet (MD) is associated with a better cardiometabolic profile, but these beneficial effects may be influenced by genetic variations, modulating the predisposition to obesity or MetS. The aim was to assess whether interaction effects occur between an obesity genetic risk score (obesity-GRS) and the MD on adiposity and MetS in European adolescents. Multiple linear regression models were used to assess the interaction effects of an obesity-GRS and the MD on adiposity and MetS and its components. Interaction effects between the MD on adiposity and MetS were observed in both sex groups ( p < 0.05). However, those interaction effects were only expressed in a certain number of adolescents, when a limited number of risk alleles were present. Regarding adiposity, a total of 51.1% males and 98.7% females had lower body mass index (BMI) as a result of higher MD adherence. Concerning MetS, only 9.9% of males with higher MD adherence had lower MetS scores. However, the same effect was observed in 95.2% of females. In conclusion, obesity-related genotypes could modulate the relationship between MD adherence and adiposity and MetS in European adolescents; the interaction effect was higher in females than in males.

Gonadal dysgenesis (GD) is a rare cause of differences of sex development (DSD) with highly variable clinical and genetic conditions. Although identification of the causative genetic alterations can offer a clearer prognosis and personalized management to patients, more than 50% of the DSD cases still do not have an accurate genetic diagnosis. NR5A1 (previously known as SF-1), is a transcriptional regulator of genes required for normal development and functional maintenance of the gonads and the adrenal glands. Nucleotide sequence variants of the NR5A1 gene have been reported in numerous patients with GD with or without adrenal failure, however, microdeletion or partial deletion in the NR5A1 gene have been described only in a few GD cases. In this case study, we present a subject with female phenotype, mild clitoromegaly, partial GD and normal adrenal function. Cytogenetic analysis revealed a 46,XY SRY + karyotype. Microarray analysis did not identify pathogenic copy number variations, nor did panel sequencing of the most common DSD genes. Subsequently, multiplex ligation-dependent probe amplification (MLPA) was performed to test for small deletion/duplication of the most frequently affected genes associated with GD. Using this method, we have identified a novel heterozygous deletion involving exons 5 and 6 of the NR5A1 gene as the cause of abnormal sexual development of the patient. This report expands our knowledge about the range and pathogenetic role of NR5A1 mutations associated with partial gonadal dysgenesis in 46,XY DSD. Furthermore, our data emphasises the indispensable role of MLPA in the diagnosis of DSD with unclear etiology.

There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX copy number variation (CNV) structures, which harbor CYP21A2, was performed. In total, 389 unrelated Hungarian individuals with European ancestry (164 healthy subjects, 125 patients with non-functioning adrenal incidentaloma and 100 patients with classical CAH) as well as 34 adrenocortical tumor specimens were studied using a set of experimental and bioinformatic methods. A unique, moderately frequent (2%) haplotypic RCCX CNV structure with three repeated segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in the 3'-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472) variant in the middle segment occurred in all c.955C>T carriers with normal steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced mRNA in the adrenal gland, confirming its functionality and ability to rescue the carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived from the 3'-segment of LBSASB after the loss of functional CYP21A2 from the middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in the studied European population. Therefore, c.*12C>T may be suitable as a marker to avoid this genetic confound and improve the diagnosis of CAH.

Objective: To assess the frequencies of common polymorphisms of genes associated with energy expenditure among Hungarian obese children and investigate their influences on obesity-related traits and metabolic complications of common childhood obesity., Research Methods and Procedures: In a total of 528 obese children (age 13.2±2.6 years) an oral glucose tolerance test and determination of fasting serum lipid levels were carried out, blood pressure and resting energy expenditure were measured and the children were genotyped for the following gene polymorphisms: Trp64Arg of β3-adrenoreceptor (ADRB3), -3826 A/G of uncoupling protein (UCP)-1, exon 8 45 bp del/ins and -866 G/A of UCP-2, -55 C/T of UCP-3, and Pro12Ala of peroxisome-proliferator activated receptor gamma-2., Results: Carriers of the ADRB3 Arg64 allele had a significantly higher relative body weight and relative body mass index compared with non-carriers. The UCP-2 exon 8 del/ins polymorphism was associated with higher degree of obesity, insulin resistance, dyslipideamia and lower adjusted metabolic rate. Children with UCP-3 -55 T/T genotype had a significantly lower adjusted metabolic rate than the C allele carriers., Conclusion: We found evidence for associations between common polymorphisms of the ADRB3, the UCP-2 and UCP-3 genes and basic metabolic rate as well as level and metabolic consequences of common obesity among Hungarian school-aged children., (Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Objective: Gln223 Arg polymorphism of the leptin receptor (LEPR) gene is one of the most frequently examined polymorphisms of this gene and has been suggested to be associated with energy expenditure (EE). The aim of the present study was to investigate the association of this variant on indicators of EE-resting metabolic rate (RMR), postabsorptive and postprandial respiratory quotient (RQ), and food-induced thermogenesis (FIT)-in obese children., Methods: The study included 486 genotyped children (obese, n = 355). RMR was measured by indirect calorimetry for 45 min. Subsequent to test-food consumption, FIT was measured in a subsample of obese children (n = 121, body mass index 31.9 kg/m(2) (mean ± SD 5.1)., Results: Obese children with the Gln223 Gln genotype showed a significantly lower post-absorptive and postprandial RQ (P = 0.0055 versus P = 0.0002, adjusted for age, sex, and lean body mass) than did groups of children with Gln223 Arg and Arg223 Arg genotypes. No significant differences were observed in FIT and RMR among the carriers and non-carriers of the 223 Arg allele., Conclusion: The significantly lower post-absorptive and postprandial RQ in the group of Gln223 Gln genotype children indicates that the fat oxidation of these children maybe increased before and subsequent to food consumption, which can be important in the planning of diet of these children., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: There are no population-based data on the autoimmune morbidity and vascular complications of young adults with childhood-onset type 1 diabetes in Hungary., Aims: To assess the prevalence of these morbidities after 20 years of diabetes duration., Method: Postal questionnaire., Results: 6.2% of the patients had celiac disease. Diabetes was diagnosed at a significantly earlier age in patients with diabetes and celiac disease as compared to those without celiac diasease. Thyroid autoimmunity was reported in 7.6% of cases. They were significantly older with longer duration of diabetes. Every fifth patients reported retinopathy, one sixth of patients was treated for hypertension. Neuropathy was found in 3.4% and kidney disease in 4.8% of the cases., Conclusions: Apart from retinopathy and hypertension, the prevalence of microvascular complications was relatively low. Considering the limitations of questionnaire studies, laboratory screening is warranted to assess the true prevalence of comorbidities and complications.