title: Lack of association between the tagging SNP A+930-->G of SOCS3 and type 2 diabetes mellitus: meta-analysis of four independent study populations.
abstract: BACKGROUND
  The suppressor of cytokine signalling 3 (SOCS3) provides a link between cytokine action and their negative consequences on insulin signalling. Thus SOCS3 is a potential candidate gene for type 2 diabetes (T2DM).
  
  
  RESULTS
  Based on HapMap we identified the polymorphism A+930-->G (rs4969168) as a haplotype tagging SNP (htSNP) sufficiently covering the genetic variation of the whole gene. We therefore examined the association between rs4969168 within SOCS3 and T2DM in three independent study populations; one prospective case-cohort study and two cross-sectional study populations. Due to the low frequency of individuals being homozygous for the polymorphism a dominant model of inheritance was assumed. The case-cohort study with 2,957 individuals (764 of them with incident T2DM) showed no effect of the polymorphism on diabetes risk (hazard ratio (95%CI): 0.86 (0.66-1.13); p = 0.3). Within the MeSyBePo-study population 325 subjects had T2DM from a total of 1,897 individuals, while the second cross-sectional cohort included 851 cases of T2DM within a total of 1653 subjects. According to the results in the prospective study, no association with T2DM was found (odds ratio (95%CI): 0.78 (0.54-1.12) for MesyBepo and 1.13 (0.90-1.42) for the Leipzig study population). There was also no association with metabolic subtraits such as insulin sensitivity (p = 0.7), insulin secretion (p = 0.8) or the hyperbolic relation of both, the disposition index (p = 0.7). In addition, no evidence for interaction with BMI or sex was found. We subsequently performed a meta-analysis, additionally including the publicly available data from the T2DM-subcohort of the WTCCC (n = 4,855). The overall odds ratio within that meta-analysis was 0.96 (0.88-1.06).
  
  
  CONCLUSIONS
  There is no strong effect of the common genetic variation within the SOCS3 gene on the development of T2DM.
authors.affiliation: Department of Endocrinology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Diabetes and Nutrition, Berlin, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Fischer-Rosinsky
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Matthias
authors.initials: M
authors.lastname: Möhlig
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
mesh_terms: D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: D007328:Insulin; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins