The co-inheritance of type 1 diabetes and multiple sclerosis in Sardinia cannot be explained by genotype variation in the HLA region alone.
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.
Centro Sclerosi Multipla, Dipartimento di Neuroscienze, University of Cagliari, Italy.
Maria Giovanna
MG
Marrosu
Costantino
C
Motzo
Raffaele
R
Murru
Rosanna
R
Lampis
Gianna
G
Costa
Patrizia
P
Zavattari
Daniela
D
Contu
Elisabetta
E
Fadda
Eleonora
E
Cocco
Francesco
F
Cucca
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007558:Italy; D009103:Multiple Sclerosis / Q000150:complications / Q000235:genetics*
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains