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; pp. 548 - 552
• Main Authors: HAEGERT, D. G, MUNTONI, F, MURRU, M. R, COSTA, G, FRANCIS, G. S, MARROSU, M. G
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-03-1993
• Subjects: Alleles; Biological and medical sciences; Canada; Disease Susceptibility; Gene Frequency; Haplotypes; HLA-DQ alpha-Chains; HLA-DQ Antigens - genetics; HLA-DQ Antigens - immunology; HLA-DQ beta-Chains; Humans; Italy; Medical sciences; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Canada; Italy; Sardinia; North America; Europe; America; Human; HLA-System; Allele; Nervous system diseases; Multiple sclerosis; French canadian; Immunological investigation; Class II histocompatibility antigen; Epidemiology; Inflammatory disease
• ISSN: 0028-3878; 1526-632X
• 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.