Impaired energy homeostasis and low-grade inflammation have been related to components of the metabolic syndrome (MetS) such as dyslipidemia, obesity, and insulin resistance. Single-nucleotide polymorphisms in the genes encoding for IL-6 (g.-634G>C; c.174G>C), TNFα (g.-308G>A), methylenetetrahydrofolate reductase (MTHFR) (c.677C>T), APOC3 (c.3175C>G), and APOA5 (g.-1131T>C) have been implicated in the processes of inflammation and energy intake that take place in the development of MetS manifestations. The aim of this study was to investigate the association between these polymorphisms and MetS, as defined by the National Cholesterol Education Program-Adult treatment Panel III criteria, in the Greek population. Overall, 30 unrelated subjects who met the criteria of MetS and 60 matched control subjects from central Greece were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. There was a significant association between both MTHFR c.677C>T (odds ratio: 4.02; confidence interval: 1.496-10.777; p=0.003) and APOA5 g.-1131T>C (odds ratio: 3.514; confidence interval: 1.065-11.585; p=0.035) and MetS. Analysis of constructed haplotypes showed a highly significant association between 677C-1131T-3175C haplotype and MetS (p<0.0001). Carriers of both MTHFR c.677T and APOA5 g.-1131C were associated with increased triglyceride levels (p=0.001 and p=0.003, respectively), compared with noncarriers. These results support a role for MTHFR and APOA5 as risk factors for MetS and suggest their further validation in larger independent populations.

2015, 14(1):126-133 Address for correspondence: Christina Kanaka-Gantenbein, MD, PhD, Associate Professor for Paediatrics Endocrinology-Juvenile Diabetes, First Department of Paediatrics, University of Athens Medical School, "Agia Sophia" Children's Hospital, Thivon & Livadias Str., GR 11527, Goudi, Athens, Greece, E-mail: chriskan@med.uoa.gr Received: 02-03-201402-03- , Accepted: 18-06-2014 Research paper epidemic. It has been estimated that in 2010, 43 million children aged <5 years were overweight or obese and that by 2020 this percentage will have risen to 60 million children.1 Contrary to prior common beliefs, it has been proved that "heavy" children will grow into unhealthy, obese adults with a plethora of medical conditions, this rendering the current epidemic a global health crisis on multiple levels. Greece has the highest percentage of overweight and obese adolescents in Europe, at 44% and 11%, respectively.

We found significantly higher Lp-PLA2 levels in obese children than lean controls. Interestingly, they all had levels >200 ng/mL, which are considered to correlate with atherosclerosis and a high thromboembolic risk in adults. The positive correlation of Lp-PLA2 with BMI suggests that Lp-PLA2 might be the link between obesity and increased cardiovascular risk, which can be elevated even at a very young age. Measurement of Lp-PLA2 in plasma could therefore represent a further biomarker for assessing increased CVD risk in obese children and adolescents.

Background: In the context of a worldwide increase in childhood obesity, euthyroid hyperthyrotropinemia has been consistently reported and raises questions about its etiology, its potential metabolic complications, and its management. In this study we analyze the thyroid function with respect to BMI, pubertal status, and sex in children with obesity and discuss our results on an integrative context with the existent data from the literature.Methods: In this case-control study, we compared 389 children and adolescents with obesity to 158 controls. Age, sex, thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), BMI standard deviation score, and pubertal status were recorded. One factor-analysis of variance (ANOVA) was used with p < 0.05.Results: Mean serum TSH of children with obesity was higher (2.95 -1.2 mU/L) compared to normal weight group (2.42 -1.43 mU/L) ( p < 0.0001). Only in females of both groups, serum TSH, T4, and T3 concentrations were all lower during puberty compared to prepuberty. In prepubertal girls and boys with obesity, a statistically significant correlation between TSH and BMI was found (r = 0.32, p = 0.012 and r = 0.47, p < 0.001, respectively), which is not sustained during puberty.Conclusions: Our results confirm the TSH elevation in children with obesity and indicates that puberty and adiposity have a differential sex-dependent impact on thyroid axis function.

Cystatin C is a non-glycosylated protein that belongs to the cystatin superfamily of cysteine protease inhibitors. Its low molecular weight (13.3kDa) and positive charge at physiological pH levels facilitates its glomerular filtration and subsequently it is reabsorbed and almost completely catabolized in the proximal renal tubules. Therefore and due to its constant rate of production, its serum concentration is determined by the rate of glomerular filtration (GFR). Cystatin C production in the body is a stable process that is not influenced by renal conditions, increased protein catabolism or dietary factors. Moreover, in contrary to creatinine, it does not change with age or muscle mass. For these reasons, serum cystatin C has been suggested to be an ideal endogenous marker of GFR. Studies on the renal function of patients with transfusion-dependent β-thalassemia are sparse. These studies suggested that the renal abnormalities observed in β-thalassemia are due to proximal tubular dysfunction and postulated that their severity is related with the degree of anemia. They were less severe in patients on hypertransfusion and appropriate desferrioxamine therapy suggesting that the damage might be caused by both anemia and increased oxidation induced by excess iron deposition. None of these studies have demonstrated renal insufficiency as reflected by decreased GFR. This was probably due to the fact that all estimations were based on creatinine measurements. In this study we estimated GFR in 195 transfused patients with β-thalassemia major by measuring cystatin C and calculating GFR according to the recently proposed cystatin C-based prediction equation using only concentration in mg/L and a prepubertal factor:1GFR [mL/min/1.73m2] = 84.7 × cystatin C (mg/L)−1.68 × 1.38* (*if a child <14 years). We found that 136 patients had normal cystatin C levels (0.66–1.03mg/L) and GFR values (80–170mL/min/1.73m2), 36 patients had mild renal insufficiency (cystatin C levels: 1.04–1.22mg/L and GFR values: 60–79mL/min/1.73m2), 21 patients had moderate renal insufficiency (cystatin C levels: 1.23–1.72mg/L and GFR values: 34–59mL/min/1.73m2), while 2 patients had severe renal insufficiency with cystatin C levels >2.5mg/L and GFR values <20mL/min/1.73m2. We further determined plasma levels of Neutrophil gelatinase-associated lipocalin (NGAL) in 30 randomly selected patients. NGAL is a protein expressed on tubular cells of which the production is markedly increased in response to harmful stimuli, such as ischemia or toxicity. We found increased NGAL levels in 19 β-thalassemia patients (mean: 95.0±45.0mg/L compared to normal values of 51.2±11.8mg/L, p<0.0003). NGAL levels correlated significantly with cystatin C levels (r=0.740, p<0.0001), indicating that the renal impairment in these patients seems to be originated from tubular injury. The findings of this study indicate that renal insufficiency is present in a significant proportion of transfusion-dependent β-thalassemia patients. Further studies are warranted in order to identify predisposing factors that contribute to the renal damage in thalassemia and to establish appropriate guidelines for the evaluation and follow up of renal function in these patients. 1. Clin Chem2005;51:1420–143.