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Evaluation of IL12B as a candidate type I diabetes susceptibility gene using data from the Type I Diabetes Genetics Consortium

Genes & Immunity volume 10, pages S64–S68 (2009)Cite this article

Abstract

As part of its efforts to identify genes affecting the risk of type I diabetes (T1D), the Type I Diabetes Genetics Consortium commissioned an extensive survey of variants associated with genes reported earlier to have an association with disease susceptibility. In this report, we present the analysis of a set of single-nucleotide polymorphisms (SNPs) within and flanking the IL12B gene, which encodes the p40 subunit of the cytokines interleukin (IL)-12 and IL-23. No SNP showed individually significant association in the population as a whole. Nevertheless, subjects stratified according to genotype at the earlier reported SNP in the IL12B 3′UTR, rs3212227, confirmed small, but significant, differences in age of disease onset with a relative hazard=0.88 (P=0.005). The protective effect of rs3212227 allele 2 was gender specific (P=0.004 overall and P=0.0003 when unaffected siblings were considered). Among females, the 2.2 genotype was more protective, with relative hazard=0.75. We conclude that while there was no major effect of IL12B polymorphisms on T1D susceptibility in the entire study group, they have an impact on a subset of at-risk individuals.

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Acknowledgements

This research uses resources provided by the Type I Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF), and supported by U01 DK062418. GM is supported by the Diabetes Research Foundation, Inc, and Program Grant #516700 from the National Health and Medical Research Council of Australia. Genotyping was performed at the Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources.

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Authors and Affiliations

  1. Centre for Diabetes Research, The Western Australian Institute for Medical Research, and Centre for Medical Research, University of Western Australia, Perth, Western Australia, Australia

    G Morahan & J Berry

  2. Centre for Clinical Immunology and Biomedical Statistics, Murdoch University and Royal Perth Hospital, Western Australia, Australia

    E McKinnon & I James

  3. The University of Auckland, Auckland, New Zealand

    B Browning

  4. Inserm 730 et CEA, Institut de Genomique Centre National de Genotypage, Evry, France

    C Julier

  5. Steno Diabetes Center, Gentofte, Denmark

    F Pociot

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  1. G Morahan
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Correspondence to G Morahan.

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Morahan, G., McKinnon, E., Berry, J. et al. Evaluation of IL12B as a candidate type I diabetes susceptibility gene using data from the Type I Diabetes Genetics Consortium. Genes Immun 10 (Suppl 1), S64–S68 (2009). https://doi.org/10.1038/gene.2009.94

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