Effect of Cytokine Signaling 3 Gene Polymorphisms in Childhood Obesity

Abstract

Objective:Although polymorphisms in suppressor of cytokine signaling 3 (SOCS3) was reported to be related to obesity, Metabolic syndrome (MS), and type 2 diabetes mellitus in various adult studies, there is a lack of data in children. In this study, we examined eight reported polymorphisms of SOCS3 in obese Turkish children and adolescent with and without MS and compared the results with that of controls.Methods:One hundred and forty eight obese and 63 age- and sex-matched control subjects were enrolled in the study. Obesity classification was carried out according to body mass index. World Health Organization and National Cholesterol Education Program criteria were used for the diagnosis of MS. Genotyping procedure was carried out by polymerase chain reaction and Sanger sequencing protocol.Results:The frequency of rs2280148 polymorphism was significantly higher in obese subjects with MS than in the control group, whereas the frequency of rs8064821 polymorphism was significantly higher in obese subjects with MS than in obese children without MS.Conclusion:The significant associations of certain SOCS3 polymorphisms with obesity parameters in both MS and MS -related insulin resistance, hypertension, and fatty liver suggest that polymorphisms in this gene may play a role in the pathogenesis of MS and also that they can be potentially used as a marker for attenuated or aggressive disease.

A 6-CpG validated methylation risk score model for metabolic syndrome: The HyperGEN and GOLDN studies

“…Independent CpGs included were cg00574958 from carnitine palmitoyl transferase 1A ( CPT1A) , cg02650017 from Phosphoethanolamine/Phosphocholine Phosphatase 1 ( PHOSPHO1 ), cg06500161 from ATP Binding Cassette Subfamily G Member 1 ( ABCG1 ), cg11024682 from Sterol Regulatory Element Binding Transcription Factor 1 ( SREBF1 ), cg18181703 from Suppressor Of Cytokine Signaling 3 ( SOCS3 ), and cg19693031 from Thioredoxin Interacting Protein ( TXNIP ). Bolstering to the validity of our CpG selection each gene has strong biological plausibility for association with MetS including roles in fatty acid metabolism ( CPT1A ) [ 17 ], lipid homeostasis and metabolism ( SREBF1 [ 18 ], ABCG1 ) [ 19 ], skeletal endocrine regulation of metabolism ( PHOSPHO1 ) [ 20 ], cytokine signaling (SOCS3) [ 21 ] and oxidative stress ( TXNIP ) [ 22 ].…”

Suppressor of Cytokine Signaling 3: Emerging Role Linking Central Insulin Resistance and Alzheimer’s Disease

“…Recently, clinical investigations have revealed that individuals with insulin resistance, or with a high risk of insulin resistance, have increased SOCS3 levels ( Ghanim et al, 2007 , 2009 ). In genetic analyses, SOCS3 polymorphisms and epigenetic methylation have also been associated with insulin resistance ( Ali et al, 2016 ; Boyraz et al, 2016 ). Based on these findings, it is reasonable to speculate that SOCS3 is involved in the development of insulin resistance in the human body and that increased levels of SOCS3 could lead to pathological conditions that disrupt the insulin signaling pathway.…”

Maternal Socs3 knockdown attenuates postnatal obesity caused by an early life environment of maternal obesity and intrauterine overnutrition in progeny mice

“…It was also shown that inhibiting Socs3 expression in skeletal muscle is an effective strategy for improving whole‐body insulin sensitivity in obesity 14 . In humans, both polymorphisms and methylation variants of the Socs3 gene were found to be associated with obesity, and methylated modifications are thought to mediate the effect of the early life environment on adult metabolism 15,16 . Although these observations suggest that SOCS3 is very important for regulating leptin resistance and energy homeostasis across generations, there is no conclusive evidence that Socs3 is an effective target for the treatment of metabolic disorders.…”