title: Contribution of a single DQ beta chain residue to multiple sclerosis in French Canadians.
abstract: Putative disease susceptibility and resistance HLA class II alleles were studied in 78 French Canadian multiple sclerosis (MS) patients and 79 controls by using sequence-specific oligonucleotide probes to analyze in vitro amplified DNA (PCR-SSOP) typing). In this relatively homogeneous ethnic group, MS was positively associated with DRB5*0101, DQB1*0602, and DQA1*0102 and negatively associated with DQB1*0301. The strongest disease association was with DQB1*0602. Complete DQB1 typing of these individuals, plus RFLP DQ beta typing of an additional five patients showed that 98% of patients compared with 73% of controls carry DQB1 alleles encoding leucine at residue 26. In contrast, 16% of patients compared with 38% of controls carry DQB1 alleles encoding tyrosine at the same residue, and 22% of patients versus 44% of controls carry DQB1 alleles encoding glycine at residue 26. The positive disease correlation was confirmed with SSO probes designed to hybridize to codons for amino acids 22-27 of DQB1*0602, 0603, 0604, 0302, 0303 or to codons for amino acids 25-31 of DQB1*0201; all of these alleles encode Leu 26. These findings suggest that DQ beta chain polymorphisms at a single residue contribute to the development of MS in the French Canadian population.
authors.affiliation: Memorial University of Newfoundland, St. John's, Canada.
authors.forename: D G
authors.initials: DG
authors.lastname: Haegert
authors.forename: G S
authors.initials: GS
authors.lastname: Francis
mesh_terms: D000483:Alleles; D001327:Autoimmune Diseases / Q000208:ethnology* / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D002170:Canada; D004198:Disease Susceptibility / Q000276:immunology; D005006:Ethnicity / Q000235:genetics; D005602:France / Q000208:ethnology; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006801:Humans; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000208:ethnology* / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C057615:HLA-DQbeta antigen