Functional SOCS1 polymorphisms are associated with variation in obesity in whites

T. Gylvin, J. Ek, R. Nolsøe, A. Albrechtsen, G. Andersen, R. Bergholdt, C. Brorsson, C. H. Bang-Berthelsen, T. Hansen, A. E. Karlsen, N. Billestrup, K. Borch-Johnsen, T. Jørgensen, O. Pedersen, T. Mandrup-Poulsen, J. Nerup, Flemming Pociot*

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review


    Aims/hypothesis: 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. Methods: 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. Results: 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. Conclusions/interpretation: This study demonstrates that functional variations in the SOCS1 promoter may associate with alterations in BMI in the general white population.

    Sider (fra-til)196-203
    Antal sider8
    TidsskriftDiabetes, Obesity and Metabolism
    Udgave nummer3
    StatusUdgivet - 1 jan. 2009


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