The aim of this study was to ascertain possible associations between childhood obesity, its anthropometric and clinical parameters, and three loci of proteasomal genes rs2277460 (PSMA6 c.-110C>A), rs1048990 (PSMA6 c.-8C>G), and rs2348071 (PSMA3 c. 543+138G>A) implicated in obesity-related diseases. Obese subjects included 94 otherwise healthy children in Latvia. Loci were genotyped and then analyzed using polymerase chain reactions, with results compared to those of 191 nonobese controls. PSMA3 SNP frequency differences between obese children and controls, while not reaching significance, suggested a trend. These differences, however, proved highly significant (P < 0.002) in the subset of children reporting a family history of obesity. Among obese children denying such history, PSMA6 c.-8C>G SNP differences, while being nonsignificant, likewise suggested a trend in comparison to the nonobese controls. No PSMA6 c.-110C>A SNP differences were detected in the obese group or its subsets. Finally, PSMA3 SNP differences were significantly associated (P < 0.05) with circulating low-density lipoprotein cholesterol (LDL) levels. Our results clearly implicate the PSMA3 gene locus as an obesity risk factor in those Latvian children with a family history of obesity. While being speculative, the clinical results are suggestive of altered circulatory LDL levels playing a possible role in the etiology of obesity in the young.

Childhood obesity carries a high risk of serious life-threatening cardiometabolic diseases in adulthood, which are associated with low-grade inflammation. The aim of the present study was to measure serum cytokine concentrations in obese children recruited during endocrinology consultations and compared to lean control the results. Blood serum concentrations of interferon gamma (IFNγ), IL-1β, Interleukin 6 IL-6, IL-10, and TNF-α were analysed applying Luminex xMap technology with Millipore reagent kits. Statistical analyses were performed using t-test comparisons and Spearman correlations. Obese children had highly significant increased levels of circulating IFNγ (p < 0.0001), IL-6 (p < 0.0001), and IL-10 (p < 0.0001), compared to lean controls. IL-1β and TNFα levels, however, were not elevated. Significant correlation of serum cytokines to per cent excess body mass was only observed with IL-6 (rs = 0.21, p < 0.03), although IL-1β (rs = 0.18, p < 0.08) results were suggestive of a trend. A significant association of obesity in childhood with serum concentrations of IFNγ, IL-6, and IL-10 is consistent with a role for low-grade inflammatory processes early in the aetiology of this disease. IL-6 further appears to be a candidate cytokine for assessment of degree of sub-acute inflammation associated with excess weight in the young.

According to the recent data the ubiquitin-proteasome system (UPS) is implicated in the pathogenesis of obesity. Aim of our study was to evaluate a possible association between genetic variations in the PSMB5 and PSMC6 genes and childhood obesity in the Latvian population. Methods. The rs11543947 (PSMB5), rs2295826 and rs2295827 (PSMC6) were genotyped in 94 overweight children versus 191 controls. Stratification was made by family history and sex. Results. Heterozygous genotype at rs11543947 (PSMB5) manifested association with the disease (P < 0.01) in total group and in patients with family history ] and OR = = 2.746 ], respectively). This genotype was observed more frequently (P < 0.05) in males with family obesity and in females without family history (P < 0.01).The heterozygotes at rs2295826 and rs2295827 showed association (P < 0.01) in obesity (OB), in patients with family history and , respectively) and in males group. The rs11543947/ rs2295826-rs2295827 multi locus genotype heterozygous at all the studied loci and the haplotype represented by the rare alleles were more frequent in obese children when compared to controls (P < 0.001 and P = 0.0001 respectively). Conclusions. Genetic variations of the PSMB5 (rs11543947) and PSMC6 (rs2295826 and rs2295827) genes can influence childhood obesity in Latvians.

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