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Polymorphic variation in the CBLB gene in human type 1 diabetes

Genes & Immunity volume 5, pages 232–235 (2004)Cite this article

Abstract

CBLB was evaluated as a candidate gene for type 1 diabetes (T1D) susceptibility based on its association with autoimmunity in animal models and its role in T-cell costimulatory signaling. Cblb is one of the two major diabetes predisposing loci in the Komeda diabetes-prone (KDP) rat. Cbl-b, a ubiquitin ligase, couples TCR-mediated stimulation with the requirement for CD28 costimulation, regulating T-cell activation. To identify variants with possible effects on gene function as well as haplotype tagging polymorphisms, the human CBLB coding region was sequenced in 16 individuals with T1D: no variants predicted to change the amino-acid sequence were identified. Seven single-nucleotide polymorphism (SNP) markers spanning the CBLB gene were genotyped in multiplex T1D families and assessed for disease association by transmission disequilibrium testing. No significant evidence of association was obtained for either individual markers or marker haplotypes.

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Acknowledgements

We thank Suna Onengut-Gumuscu for assistance with TDT and LD analyses, V Anne Morrison and Lemuel Navarro for assistance with nucleotide sequencing, and Mary West for manuscript preparation. This work was supported by grants from the NIH (DK46635) and JDRF (1-2001-433) to PC and from the Ministry of Education, Culture, Sports, Science and Technology of Japan to SS and NY. RK was supported by a Genome Training Grant (NHGRI, T32 HG00035).

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Authors and Affiliations

  1. Molecular Genetics Program, Benaroya Research Institute, Seattle, WA, USA

    R Kosoy & P Concannon

  2. Department of Immunology, University of Washington School of Medicine, Seattle, WA, USA

    R Kosoy & P Concannon

  3. Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    N Yokoi & S Seino

  4. Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

    S Seino

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  1. R Kosoy
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Correspondence to P Concannon.

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Kosoy, R., Yokoi, N., Seino, S. et al. Polymorphic variation in the CBLB gene in human type 1 diabetes. Genes Immun 5, 232–235 (2004). https://doi.org/10.1038/sj.gene.6364057

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