HLA-DQA1 and -DQB1 associations with multiple sclerosis in Sardinia and French Canada: evidence for immunogenetically distinct patient groups.
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.
Haegert
D G
DG
Discipline of Pathology, Memorial University of Newfoundland, St. John's, Canada.
Muntoni
F
F
Murru
M R
MR
Costa
G
G
Francis
G S
GS
Marrosu
M G
MG
D000483:Alleles; D002170:Canada; D004198:Disease Susceptibility; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D006801:Humans; D007558:Italy; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen