Human Molecular Genetics Advance Access originally published online on October 7, 2004
Human Molecular Genetics 2004 13(23):2919-2924; doi:10.1093/hmg/ddh319
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Human Molecular Genetics, Vol. 13, No. 23 © Oxford University Press 2004; all rights reserved
The co-inheritance of type 1 diabetes and multiple sclerosis in Sardinia cannot be explained by genotype variation in the HLA region alone
1Centro Sclerosi Multipla, Dipartimento di Neuroscienze and 2Laboratorio di Immunogenetica, Dipartimento di Scienze Biomediche e Biotecnologie, University of Cagliari, Italy and 3Centro di Genetica Clinica, Dipartimento di Scienze Biomediche, University of Sassari, Italy
Received June 23, 2004; Revised August 30, 2004; Accepted September 26, 2004
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 5-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. On the basis of the absolute risks for T1D of the HLA-DRB1-DQB1 genotypes, we established that these loci would only contribute to a 2-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.
* To whom correspondence should be addressed at: Dipartimento di Scienze Biomediche e Biotecnologie, University of Cagliari, Via Jenner, Cagliari 09121, Italy. Tel: +39 0706095681; Fax: +39 0706095558; Email: fcucca{at}mcweb.unica.it
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