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Human Molecular Genetics Advance Access published online on October 7, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh319
© 2004 by Oxford University Press
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Article

The co-inheritance of Type 1 Diabetes and Multiple Sclerosis in Sardinia cannot be explained by genotype variation in the HLA region alone

Maria Giovanna Marrosu 1, Costantino Motzo 2, Raffaele Murru 1, Rosanna Lampis 2, Gianna Costa 1, Patrizia Zavattari 2, Daniela Contu 2, Elisabetta Fadda 1, Eleonora Cocco 1, and Francesco Cucca 3*

1 Centro Sclerosi Multipla, Dipartimento di Neuroscienze, University of Cagliari, Italy
2 Laboratorio di Immunogenetica, Dipartimento di Scienze Biomediche e Biotecnologie, University of Cagliari, Italy
3 Laboratorio di Immunogenetica, Dipartimento di Scienze Biomediche e Biotecnologie, University of Cagliari, Via Jenner, Cagliari 09121, Italy; Centro di Genetica Clinica, Dipartimento di Scienze Biomediche, University of Sassari, Italy

* To whom correspondence should be addressed. E-mail: fcucca{at}mcweb.unica.it.


  Abstract

Type 1 Diabetes (T1D) and Multiple Sclerosis (MS) are two autoimmune diseases which exhibit a considerably higher incidence in Sardinia compared with the surrounding Southern-European populations. Surprisingly, a five-fold increased prevalence of T1D has also been observed in Sardinian MS patients. Susceptibility to both disorders is associated with common variants of the HLA-DRB1 and -DQB1 loci. In this study we determined the relative contribution of genotype variation of these loci to the co-occurrence of the two disorders in Sardinia. We genotyped 1052 T1D patients and 1049 MS patients (31 of whom also had T1D) together with 1917 ethnically matched controls. Based on the absolute risks for T1D of the HLA-DRB1-DQB1 genotypes we established that these loci would only contributed to a two-fold increase in T1D prevalence in MS patients. From this evidence we conclude that shared disease associations due to the HLA-DRB1-DQB1 loci provide only a partial explanation for the observed increased prevalence of T1D in Sardinian MS patients. The data suggest that variation at other non-HLA class II loci and/or unknown environmental factors contribute significantly to the co-occurrence of these two traits.


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