Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Mar;60(3):1041-4.
doi: 10.2337/db10-0446. Epub 2011 Jan 26.

An allele of IKZF1 (Ikaros) conferring susceptibility to childhood acute lymphoblastic leukemia protects against type 1 diabetes

Austin D-E Swafford  1 , Joanna M M Howson, Lucy J Davison, Chris Wallace, Deborah J Smyth, Helen Schuilenburg, Meeta Maisuria-Armer, Trupti Mistry, Michael J Lenardo, John A Todd
Affiliations

An allele of IKZF1 (Ikaros) conferring susceptibility to childhood acute lymphoblastic leukemia protects against type 1 diabetes

Austin D-E Swafford et al. Diabetes. 2011 Mar.

Abstract

Objective: IKZF1 encoding Ikaros, an essential regulator of lymphopoiesis and immune homeostasis, has been implicated in the development of childhood acute lymphoblastic leukemia (C-ALL). Because recent genome-wide association (GWA) studies have linked a region of the 3'-UTR of IKZF1 with C-ALL susceptibility, we tested whether IKZF1 is associated with the autoimmune disease type 1 diabetes.

Research design and methods: rs10272724 (T>C) near IKZF1 at 7p12 was genotyped in 8,333 individuals with type 1 diabetes, 9,947 control subjects, and 3,997 families of European ancestry. Association was tested using logistic regression in the case-control data and by the transmission disequilibrium test in the families. Expression data for IKZF1 by rs10272724 genotype were obtained using quantitative PCR of mRNA/cDNA generated from peripheral blood mononuclear cells from 88 individuals, whereas expression data for five other neighboring genes were obtained from the online Genevar dataset.

Results: The minor allele of rs10272724 (C) was found to be protective from type 1 diabetes (odds ratio 0.87 [95% CI 0.83-0.91]; P = 1.1 × 10(-11)). rs10272724 was not correlated with levels of two transcripts of IKZF1 in peripheral blood mononuclear cells.

Conclusions: The major susceptibility genotype for C-ALL confers protection from type 1 diabetes. Our finding strengthens the link between autoimmunity and lymphoid cancers. Further investigation is warranted for the genetic effect marked by rs10272724, its impact on IKZF1, and the role of Ikaros and other family members, Ailios (IKZF3) and Eos (IKZF4), in autoimmunity.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Association of IKZF1 expression with rs10272724 (T>C) genotype in 88 unaffected individuals. A: qPCR analysis of IKZF1 Isoform 1 transcript expression. B: qPCR analysis of IKZF1 Isoform 2 transcript expression. δCt were calculated using the IKZF1 Isoform 1 or Isoform 2 qPCR Ct value minus the single copy gene β2 microglobulin (B2M) qPCR Ct value. Expression values were compared via one-way ANOVA using Prism software.
See this image and copyright information in PMC

References

    1. Winandy S, Wu L, Wang JH, Georgopoulos K. Pre-T cell receptor (TCR) and TCR-controlled checkpoints in T cell differentiation are set by Ikaros. J Exp Med 1999;190:1039–1048 - PMC - PubMed
    1. Umetsu SE, Winandy S. Ikaros is a regulator of Il10 expression in CD4+ T cells. J Immunol 2009;183:5518–5525 - PMC - PubMed
    1. Georgopoulos K. Haematopoietic cell-fate decisions, chromatin regulation and ikaros. Nat Rev Immunol 2002;2:162–174 - PubMed
    1. Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med 2004;350:1535–1548 - PubMed
    1. Martinelli G, Iacobucci I, Storlazzi CT, et al. IKZF1 (Ikaros) deletions in BCR-ABL1-positive acute lymphoblastic leukemia are associated with short disease-free survival and high rate of cumulative incidence of relapse: a GIMEMA AL WP report. J Clin Oncol 2009;27:5202–5207 - PubMed

Publication types

Substances