title: Functional SOCS1 polymorphisms are associated with variation in obesity in whites.
abstract: OBJECTIVE
  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
  This study demonstrates that functional variations in the SOCS1 promoter may associate with alterations in BMI in the general white population.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Gylvin
authors.forename: J
authors.initials: J
authors.lastname: Ek
authors.forename: R
authors.initials: R
authors.lastname: Nolsøe
authors.forename: A
authors.initials: A
authors.lastname: Albrechtsen
authors.forename: G
authors.initials: G
authors.lastname: Andersen
authors.forename: R
authors.initials: R
authors.lastname: Bergholdt
authors.forename: C
authors.initials: C
authors.lastname: Brorsson
authors.forename: C H
authors.initials: CH
authors.lastname: Bang-Berthelsen
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: A E
authors.initials: AE
authors.lastname: Karlsen
authors.forename: N
authors.initials: N
authors.lastname: Billestrup
authors.forename: K
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: T
authors.initials: T
authors.lastname: Jørgensen
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
authors.forename: T
authors.initials: T
authors.lastname: Mandrup-Poulsen
authors.forename: J
authors.initials: J
authors.lastname: Nerup
authors.forename: F
authors.initials: F
authors.lastname: Pociot
mesh_terms: D000328:Adult; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics*
chemical_list: C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins