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
- Daniela Contu1,
- Laura Morelli2,
- Patrizia Zavattari1,
- Rosanna Lampis1,
- Efisio Angius3,
- Paola Frongia3,
- Daniela Murru1,
- Mario Maioli4,
- Paolo Francalacci2,
- John A. Todd5 and
- Francesco Cucca1
- 1Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Ospedale Microcitemico, Cagliari, Italy
- 2Dipartimento di Zoologia e Antropologia Biologica, Università di Sassari, Sassari, Italy
- 3Servizio di Diabetologia Pediatrica, Ospedale G. Brotzu, Cagliari, Italy
- 4Istituto di Clinica Medica, Servizio di Diabetologia, Università di Sassari, Sassari, Italy
- 5Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K
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.
Address correspondence and reprint requests to Francesco Cucca, Dipartimento di Scienze Biomediche e Biotecnologie, University of Cagliari, Via Jenner, Cagliari 09121, Italy. E-mail:.
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.