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Lack of Association between the Tagging SNP A+930→G of SOCS3 and Type 2 Diabetes Mellitus: Meta-Analysis of Four Independent Study Populations

Author

Listed:
  • Antje Fischer-Rosinsky
  • Eva Fisher
  • Peter Kovacs
  • Matthias Blüher
  • Matthias Möhlig
  • Andreas F H Pfeiffer
  • Heiner Boeing
  • Joachim Spranger

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). Methodology/Principal Findings: 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/Significance: There is no strong effect of the common genetic variation within the SOCS3 gene on the development of T2DM.

Suggested Citation

  • Antje Fischer-Rosinsky & Eva Fisher & Peter Kovacs & Matthias Blüher & Matthias Möhlig & Andreas F H Pfeiffer & Heiner Boeing & Joachim Spranger, 2008. "Lack of Association between the Tagging SNP A+930→G of SOCS3 and Type 2 Diabetes Mellitus: Meta-Analysis of Four Independent Study Populations," PLOS ONE, Public Library of Science, vol. 3(12), pages 1-4, December.
    • Handle: RePEc:plo:pone00:0003852
    DOI: 10.1371/journal.pone.0003852
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    Cited by:

    1. Bei-Bei Zhang & Xing-Zhen Liu & Jin Sun & Yan-Wei Yin & Qian-Qian Sun, 2013. "Association between TNF α Gene Polymorphisms and the Risk of Duodenal Ulcer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(2), pages 1-7, February.
    2. Bing-Hu Li & Li-Li Zhang & Bei-Bei Zhang & Yan-Wei Yin & Li-Meng Dai & Yan Pi & Lu Guo & Chang-Yue Gao & Chuan-Qin Fang & Jing-Zhou Wang & Jing-Cheng Li, 2013. "Association between NADPH Oxidase p22phox C242T Polymorphism and Ischemic Cerebrovascular Disease: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(2), pages 1-8, February.

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