Sex-Related Bias and Exclusion Mapping of the Nonrecombinant Portion of Chromosome Y in Human Type 1 Diabetes in the Isolated Founder Population of Sardinia

  1. Daniela Contu1,
  2. Laura Morelli2,
  3. Patrizia Zavattari1,
  4. Rosanna Lampis1,
  5. Efisio Angius3,
  6. Paola Frongia3,
  7. Daniela Murru1,
  8. Mario Maioli4,
  9. Paolo Francalacci2,
  10. John A. Todd5 and
  11. Francesco Cucca1
  1. 1Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Ospedale Microcitemico, Cagliari, Italy
  2. 2Dipartimento di Zoologia e Antropologia Biologica, Università di Sassari, Sassari, Italy
  3. 3Servizio di Diabetologia Pediatrica, Ospedale G. Brotzu, Cagliari, Italy
  4. 4Istituto di Clinica Medica, Servizio di Diabetologia, Università di Sassari, Sassari, Italy
  5. 5Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K

    Abstract

    A male excess in Sardinian type 1 diabetic cases has previously been reported and was largely restricted to those patients carrying the HLA-DR3/nonDR4 genotype. In the present study, we have measured the male- to-female (M:F) ratio in a sample set of 542 newly collected, early-onset type 1 diabetic Sardinian patients. This data not only confirm the excess of male type 1 diabetic patients overall (M:F ratio = 1.3, P = 3.9 × 10−3) but also that the bias in male incidence is largely confined to patients with the DR3/nonDR4 genotype (M:F ratio = 1.6, P = 2.0 × 10−4). These sex effects could be due to a role for allelic variation of the Y chromosome in the susceptibility to type 1 diabetes, but to date this chromosome has not been evaluated in type 1 diabetes. We, therefore, established the frequencies of the various chromosome Y lineages and haplotypes in 325 Sardinian male patients, which included 180 cases with the DR3/nonDR4 genotype, and 366 Sardinian male control subjects. Our results do not support a significant involvement of the Y chromosome in DR3/nonDR4 type 1 diabetic cases nor in early-onset type 1 diabetes as a whole. Other explanations, such as X chromosome-linked inheritance, are thus required for the male bias in incidence in type 1 diabetes in Sardinia.

    Footnotes

    • Address correspondence and reprint requests to Francesco Cucca, Dipartimento di Scienze Biomediche e Biotecnologie, University of Cagliari, Via Jenner, Cagliari 09121, Italy. E-mail: fcucca{at}mcweb.unica.it.

      Received for publication 10 June 2002 and accepted in revised form 26 August 2002.

      D.C. and L.M. contributed equally to this article.

      M:F, male-to-female; NRY, nonrecombinant portion of chromosome Y.

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