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Original Articles

An Explanation for the Neutral Effect of DR2 on IDDM Susceptibility in Central Italy

  1. Rosa Sorrentino,
  2. Ugo De Grazia,
  3. Raffaella Buzzetti,
  4. Lorenza Nistico,
  5. Carlo Iannicola,
  6. Sandro Costanzi and
  7. Roberto Tosi
  1. Department of Cell Biology and Development, University La Sapienza Rome, Italy Institute of Cell Biology, CNR Rome, Italy II Clinica Medica, Università La Sapienza, Policlinico Umberto I Roma Chair of Medical Genetics, University La Sapienza, Ospedale Spallanzani Rome, Italy
  1. Address correspondence and reprint requests to Roberto Tosi, Istituto di Biologia Cellulare, Viale Marx 43, 00137 Roma, Italy.
Diabetes 1992 Aug; 41(8): 904-908. https://doi.org/10.2337/diab.41.8.904
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Abstract

Susceptibility to IDDM is strongly associated with HLA. Some HLA allelic combinations (haplotypes) can be found in most patients, whereas other haplotypes are encountered only rarely. It has been proposed that this difference in susceptibility depends on the absence (in the DR3 and DR4 haplotypes) or the presence (in the DR2 haplotype) of Asp57 in the DQ β-chain. Data on southern European populations challenge this hypothesis because the DR2 haplotype has not been associated negatively with IDDM, as reported in northern European populations. This study on a selected panel of DR2-positive Italian IDDM patients shows that 19 of 21 (90.5%) DR2 haplotypes possess a non-Asp57 DQB allele. Moreover, the same non-Asp57 subtype has a comparatively high frequency (9/28, or 32.1%, DR2 haplotypes) also in the DR2-positive healthy Italian population. The difference between patients and control subjects is significant (xP < 0.0001). This is the largest series of DR2-positive patients analyzed so far. Comparison with cumulated data in various white populations shows a distinct northern European-to-southern European gradient. Toward southern Europe, the relative frequency of the non-Asp57 DR2 subtype increases. Concomitantly, the apparent protective effect of the DR2 haplotype disappears. Therefore, the observed differences in DR2-IDDM association in white populations can be explained adequately by the Asp57 hypothesis, which this study's data strongly support.

  • Received September 19, 1991.
  • Revision received March 30, 1992.
  • Accepted March 30, 1992.
  • Copyright © 1992 by the American Diabetes Association
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August 1992, 41(8)
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An Explanation for the Neutral Effect of DR2 on IDDM Susceptibility in Central Italy
Rosa Sorrentino, Ugo De Grazia, Raffaella Buzzetti, Lorenza Nistico, Carlo Iannicola, Sandro Costanzi, Roberto Tosi
Diabetes Aug 1992, 41 (8) 904-908; DOI: 10.2337/diab.41.8.904

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An Explanation for the Neutral Effect of DR2 on IDDM Susceptibility in Central Italy
Rosa Sorrentino, Ugo De Grazia, Raffaella Buzzetti, Lorenza Nistico, Carlo Iannicola, Sandro Costanzi, Roberto Tosi
Diabetes Aug 1992, 41 (8) 904-908; DOI: 10.2337/diab.41.8.904
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