Contribution of a single DQ beta chain residue to multiple sclerosis in French Canadians

• Published in: Human immunology Vol. 34; no. 2; p. 85
• Main Authors: Haegert, D G, Francis, G S
• Format: Journal Article
• Language: English
• Published: United States 01-06-1992
• Subjects: Alleles; Autoimmune Diseases - ethnology; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Base Sequence; Canada; Disease Susceptibility - immunology; Ethnic Groups - genetics; France - ethnology; Gene Frequency; Genes, MHC Class II; Genetic Predisposition to Disease; HLA-DQ Antigens - genetics; HLA-DQ Antigens - immunology; HLA-DQ beta-Chains; Humans; Molecular Sequence Data; Multiple Sclerosis - ethnology; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; Polymerase Chain Reaction; France; Canada
• ISSN: 0198-8859
• DOI: 10.1016/0198-8859(92)90033-J

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.