Analysis of sequence variations in the suppressor of cytokine signaling (SOCS)-3 gene in extremely obese children and adolescents

BACKGROUND: The suppressor of cytokine signaling (SOCS)-3 is a negative feedback regulator of cytokine signaling and also influences leptin signaling. We investigated association of variations in the coding sequence and promoter region of SOCS3 with extreme obesity in German children and adolescents. METHODS: An initial screen for sequence variations in 181 extremely obese children and adolescents and 188 healthy underweight adults revealed two previously reported single nucleotide polymorphisms (SNPs) in the SOCS3 5' region: -1044 C>A (numbering refers to bases upstream of ATG in exon 2) within a predicted STAT3 binding element and -920 C>A (rs12953258, for numbering, see above). RESULTS: We did not detect significant differences in allele or genotype frequencies for any of these SNPs between the analysed study groups (all nominal p > 0.2). In addition, we performed a pedigree transmission disequilibrium test (PDT) for the SNP -1044 C>A in families comprising 703 obese children and adolescents, 281 of their obese siblings and both biological parents. The PDT revealed no transmission disequilibrium (nominal p > 0.05). CONCLUSION: In conclusion, our data do not suggest evidence for a major role of the respective SNPs in SOCS3 in the pathogenesis of extreme obesity in our study groups

Common polymorphisms in SOCS3 are not associated with body weight, insulin sensitivity or lipid profile in normal female twins

AIMS/HYPOTHESIS: Inhibition of signal transduction by suppressor of cytokine signalling-3 (SOCS-3) potentially influences resistance to insulin and leptin. We have tested association between three SNPs, rs4969169, rs12953258 and rs8064821, representing common linkage disequilibrium clusters in the SOCS3 gene, and obesity measures, insulin sensitivity measures and serum lipids in the general population. METHODS: Three SNPs, rs4969169, rs12953258 and rs8064821, with rare allele frequencies >6% were genotyped in 2777 Caucasian female twins (mean age 47.4±12.5 years) from the St Thomas’ UK Adult Twin Registry (Twins UK). RESULTS: Minor allele frequencies were as follows: rs4969169 (0.067), rs12953258 (0.097) and rs8064821 (0.101). Individual SOCS3 SNPs were not associated with general and central obesity, or with two indices of insulin sensitivity (HOMA and SiM). CONCLUSIONS/INTERPRETATIONS: We have not established any direct associations between three SNPs in the SOCS3 gene and obesity, insulin or lipid measures in this study