期刊
DIABETES
卷 60, 期 3, 页码 1041-1044出版社
AMER DIABETES ASSOC
DOI: 10.2337/db10-0446
关键词
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资金
- Juvenile Diabetes Research Foundation International (JDRF)
- Wellcome Trust [089989, 079895, 068545/Z102, 076113/C/04/Z, 076113]
- National Institute for Health Research Cambridge Biomedical Research Centre
- National Science Foundation
- National Institutes of Health Division of Intramural Research
- U.K. Medical Research Council [G0000934]
- Wellcome Trust/JDRF [061858]
- National Institutes of Health Research of England
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- National Human Genome Research Institute
- National Institute of Child Health and Human Development
- Juvenile Diabetes Research Foundation [U01 DK062418]
- British Heart Foundation [RG/08/014/24067] Funding Source: researchfish
- Medical Research Council [G0000934] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10275] Funding Source: researchfish
- MRC [G0000934] Funding Source: UKRI
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 X 10(-11)). rs10272724 was not correlated with levels of two transcripts of TKZF1 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. Diabetes 60:1041-1044, 2011
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