Functional SOCS1 polymorphisms are associated with variation in obesity in whites

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The suppressor of cytokine signalling 1 (SOCS1) is a natural inhibitor of cytokine and insulin signalling pathways and may also play a role in obesity. In addition, SOCS1 is considered a candidate gene in the pathogenesis of both type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective was to perform mutation analysis of SOCS1 and to test the identified variations for association to T2D-related quantitative traits, T2D or T1D. Mutation scanning was performed by direct sequencing in 27 white Danish subjects. Genotyping was carried out by TaqMan allelic discrimination. A total of more than 8100 individuals were genotyped. Eight variations were identified in the 5' untranslated region (UTR) region. Two of these had allele frequencies below 1% and were not further examined. The six other variants were analysed in groups of T1D families (n = 1461 subjects) and T2D patients (n = 1430), glucose tolerant first-degree relatives of T2D patients (n = 212) and normal glucose tolerant (NGT) subjects. The rs33977706 polymorphism (-820G > T) was associated with a lower body mass index (BMI) (p = 0.004). In a second study (n = 4625 NGT subjects), significant associations of both the rs33977706 and the rs243330 (-1656G > A) variants to obesity were found (p = 0.047 and p = 0.015) respectively. The rs33977706 affected both binding of a nuclear protein to and the transcriptional activity of the SOCS1 promoter, indicating a relationship between this polymorphism and gene regulation. This study demonstrates that functional variations in the SOCS1 promoter may associate with alterations in BMI in the general white population.


  • T. Gylvin
  • J. Ek
  • R. Nolsoe
  • A. Albrechtsen
  • G. Andersen
  • R. Bergholdt
  • C. Brorsson
  • C. H. Bang-Berthelsen
  • T. Hansen
  • A E Karlsen
  • N. Billestrup
  • K. Borch-Johnsen
  • T. Jorgensen
  • O. Pedersen
  • T. Mandrup-Poulsen
  • Jörn Nerup
  • Flemming Pociot
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • promoter activity, SOCS, obesity, insulin, EMSA, cytokines, diabetes
Original languageEnglish
Pages (from-to)196-203
JournalDiabetes, Obesity and Metabolism
Issue number3
Publication statusPublished - 2009
Publication categoryResearch