HLA-DQ haplotypes differ by ethnicity in patients with childhood-onset diabetes

Corresponding Author

Rebecca B Lipton

Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA

Department of Health Studies, University of Chicago, Chicago, IL 60637, USA

Rebecca B Lipton, PhD, 5841 S. Maryland Ave. MC 5053, Chicago, IL 60637, USA.
Tel: 773-834-8313;
fax: 773-702-0443;
e-mail: [email protected]Search for more papers by this author

Melinda Drum,

Melinda Drum

Department of Health Studies, University of Chicago, Chicago, IL 60637, USA

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Siri Atma W Greeley,

Siri Atma W Greeley

Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA

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Kirstie K Danielson,

Kirstie K Danielson

Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA

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Graeme I Bell,

Graeme I Bell

Department of Medicine, University of Chicago, Chicago, IL 60637, USA

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William A Hagopian,

William A Hagopian

Pacific Northwest Research Institute, Seattle, WA, USA

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Rebecca B Lipton,

Corresponding Author

Rebecca B Lipton

Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA

Department of Health Studies, University of Chicago, Chicago, IL 60637, USA

Rebecca B Lipton, PhD, 5841 S. Maryland Ave. MC 5053, Chicago, IL 60637, USA.
Tel: 773-834-8313;
fax: 773-702-0443;
e-mail: [email protected]Search for more papers by this author

Melinda Drum,

Melinda Drum

Department of Health Studies, University of Chicago, Chicago, IL 60637, USA

Search for more papers by this author

Siri Atma W Greeley,

Siri Atma W Greeley

Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA

Search for more papers by this author

Kirstie K Danielson,

Kirstie K Danielson

Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA

Search for more papers by this author

Graeme I Bell,

Graeme I Bell

Department of Medicine, University of Chicago, Chicago, IL 60637, USA

Search for more papers by this author

William A Hagopian,

William A Hagopian

Pacific Northwest Research Institute, Seattle, WA, USA

Search for more papers by this author

First published: 21 March 2011

https://doi.org/10.1111/j.1399-5448.2010.00712.x

Citations: 12

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Abstract

Lipton RB, Drum M, Greeley SAW, Danielson KK, Bell GI, Hagopian WA. HLA-DQ haplotypes differ by ethnicity in patients with childhood-onset diabetes.

Aim: To understand the etiology of childhood-onset diabetes, we examined genetic risk markers, autoantibodies, and β-cell function in a mixed race group of young patients.

Methods: One hundred and forty-five patients aged 0–17 at diagnosis (54% African American, 22% Caucasian, 16% Latino, 8% mixed-other) were studied at mean duration 6.9 ± 5.7 (range 0.1–28.5) yr, including human leukocyte antigen (HLA)-DQA1-DQB1 genotyping, stimulated C peptide (CP), glutamic acid decarboxylase, and insulinoma-associated antigen 2 antibodies (ABs). Based on no residual β-cell function (CP-) and islet autoantibodies (AB+), 111 patients were classified with type 1 diabetes mellitus (T1DM), 22 were CP+ and AB- and thus considered to have type 2 diabetes mellitus (T2DM), and 12 patients had features of both T1DM and T2DM or mixed phenotype.

Results: Based on the presence of two high-risk HLA-DQA1/B1 haplotypes, 39% of African Americans, 81% of Caucasians, 70% of Latinos, and 67% of mixed-others were at high genetic risk. In patients with T1DM, 41% of African Americans, 80% of Caucasians, 73% of Latinos, and 63% of mixed-others were genetically susceptible. Thirty-one percent of African Americans, including 29% of those with T1DM, could not be characterized because their haplotypes had unknown T1DM associations. These unusual haplotypes comprised 11% in T1DM, 14% in T2DM, and 8% in patients with mixed phenotype.

Conclusions: Fifty-nine percent of childhood-onset patients with T1DM were identified with high genetic risk based on known HLA-DQA1/B1 associations. Many non-Caucasian patients carry HLA-DQ alleles whose association with T1DM is undetermined. Genetic approaches can provide insights into the etiology and appropriate treatment of childhood-onset diabetes but only if sufficient data are available in diverse ethnic groups.

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