HLA-DQA1 and -DQB1 associations with multiple sclerosis in Sardinia and French Canada: evidence for immunogenetically distinct patient groups

• Published in: Neurology Vol. 43; no. 3 Pt 1; p. 548
• Main Authors: Haegert, D G, Muntoni, F, Murru, M R, Costa, G, Francis, G S, Marrosu, M G
• Format: Journal Article
• Language: English
• Published: United States 01.03.1993
• Subjects: Alleles; Canada; Disease Susceptibility; Gene Frequency; Haplotypes; HLA-DQ alpha-Chains; HLA-DQ Antigens - genetics; HLA-DQ Antigens - immunology; HLA-DQ beta-Chains; Humans; Italy; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; Canada; Italy
• ISSN: 0028-3878
• DOI: 10.1212/wnl.43.3_part_1.548

We analyzed the association of HLA-DQA1 and -DQB1 alleles with multiple sclerosis (MS) in a collaborative study of 116 Sardinian and 75 French Canadian MS patients by the relative predispositional effect method. In French Canadians, MS was positively associated with DQA1*0102 and DQB1*0602, but there was no positive association of either allele with Sardinian MS, which, by contrast, was positively associated with DQB1*0302 and *0201 and with DQA1*0301, whereas none of these alleles was MS-associated in French Canadians. In comparison with French Canadian results, DQA1*0102 was protective against MS in Sardinians. We suggest that DQA1*0102 has no MS predispositional role in French Canadians, but is MS-associated because it is in linkage disequilibrium with true predispositional alleles present within the DQB1*0602-bearing haplotype. Whereas DQB1 alleles encoding leucine (Leu) at residue 26 showed a strong MS association in French Canadians (relative risk = 24.7), there was no correlation with DQ beta Leu26 in Sardinian MS. No other DQA1 or DQB1 codons showed a positive disease correlation in both groups. Together the data suggest that the two MS patient groups are immunogenetically distinct, and it may be impossible to formulate a unifying hypothesis that explains the different MS-class II associations in these and other ethnic groups.