HLA-DQB1 alleles confer susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM). We investigated whether the susceptibility alleles DQB1*0302 and DQB1*0201 affect progression to diabetes among islet cell antibody–positive (ICA+) first-degree relatives of IDDM patients and whether the protective allele DQB1*0602 can be found and is still protective among such relatives. We human leukocyte antigen–typed and periodically tested β-cell function (first-phase insulin release [FPIR] during the intravenous glucose tolerance test) in 72 ICA+ relatives, of whom 30 became diabetic on follow-up (longest follow-up 12 years); 54 (75%) relatives carried DQB1*0302 and/or DQB1*0201. The frequency of DQB1*0302 and DQB1*0201 and of the high-risk genotype DQB1*0302/DQB1*0201 did not differ significantly between diabetic relatives and those remaining nondiabetic. On follow-up, progression to IDDM was not statistically different for relatives with or without the DQB1*0302/DQB1*0201 genotype. However, those relatives with the DQB1*0302/DQB1*0201 genotype had a tendency to develop diabetes at an earlier age (log-rank P = 0.02). We found DQB1*0602 in 8 of 72 (11.1%) ICA+ relatives. Relatives with DQB1*0602 did not develop diabetes or show any decline of FPIR versus 28 of 64 DQB1*0602– relatives who developed IDDM (log-rank P = 0.006; Wilcoxon's P = 0.02). The protective allele DQB1*0602 is found in ICA+ relatives who have minimal risk of progression to IDDM. Therefore, DQB1*0602 is associated with protection from IDDM both in population studies and among relatives with evidence of autoimmunity who should not enter prevention trials.
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June 01 1995
HLA-DQB1*0602 Is Associated With Dominant Protection From Diabetes Even Among Islet Cell Antibody–Positive First-Degree Relatives of Patients with IDDM
Alberto Pugliese;
Alberto Pugliese
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center
Denver, Colorado
Diabetes Research Institute, University of Miami
Miami, Florida
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Roberto Gianani;
Roberto Gianani
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center
Denver, Colorado
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Rocio Moromisato;
Rocio Moromisato
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center
Denver, Colorado
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Zuheir L Awdeh;
Zuheir L Awdeh
Center for Blood Research, Harvard Medical School
Boston, Massachusetts
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Chester A Alper;
Chester A Alper
Center for Blood Research, Harvard Medical School
Boston, Massachusetts
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Henry A Erlich;
Henry A Erlich
Human Genetics Department, Roche Molecular Systems
Alameda, California
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Richard A Jackson;
Richard A Jackson
Joslin Diabetes Center, Harvard Medical School
Boston, Massachusetts
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George S Eisenbarth
George S Eisenbarth
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center
Denver, Colorado
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Address correspondence and reprint requests to Dr. George S. Eisenbarth, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Box B-140, Denver, CO 80262.
Diabetes 1995;44(6):608–613
Article history
Received:
May 19 1994
Revision Received:
February 06 1995
Accepted:
February 06 1995
PubMed:
7789622
Citation
Alberto Pugliese, Roberto Gianani, Rocio Moromisato, Zuheir L Awdeh, Chester A Alper, Henry A Erlich, Richard A Jackson, George S Eisenbarth; HLA-DQB1*0602 Is Associated With Dominant Protection From Diabetes Even Among Islet Cell Antibody–Positive First-Degree Relatives of Patients with IDDM. Diabetes 1 June 1995; 44 (6): 608–613. https://doi.org/10.2337/diab.44.6.608
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