title: C4A gene deletion: association with Graves' disease.
abstract: The association of HLA class I and class II antigens, particularly HLA-B8,DR3, with a variety of autoimmune diseases has been well documented. The C4A*Q0 (non-expressed C4A) allele which is in linkage disequilibrium with HLA-B8,DR3 has also been reported to be associated with systemic lupus erythematosus, insulin-dependent diabetes mellitus and Graves' disease. However, the number of studies has been limited by the requirement of family data for the assignment of the C4A*Q0 allele based on C4 protein typing. Recently, with the availability of a C4 cDNA probe, a C4A gene deletion associated with HLA-B8,DR3 has been reported in normal individuals. We have tried to resolve the problem of assigning the C4A*Q0 allele by using both phenotypic and genotypic approaches and have determined the significance of the C4A*Q0 allele in 80 unrelated patients with Graves' disease and in 50 normal control subjects. Our results demonstrate a strong association of the C4A*Q0 allele with Graves' disease (56 versus 26%; P less than 0.002, relative risk = 3.7) and in particular in association with HLA-B8 and/or DR3 (92 versus 70.6%; P less than 0.04) when compared with normal controls. All the C4A*Q0 alleles that were associated with HLA-B8 and/or DR3 were due to a C4A gene deletion. Of the C4A*Q0 alleles, in Graves' disease, 94% (compared with 82% in the control group) could be detected by C4 DNA analysis using either TaqI or EcoRI restriction endonucleases. It is suggested that a combination of C4 protein typing with C4 DNA analysis is the best approach for the determination of the C4A*Q0 allele in unrelated individuals without access to family data.
authors.affiliation: Department of Medicine, King's College Hospital Medical School, Denmark Hill, London.
authors.forename: S
authors.initials: S
authors.lastname: Ratanachaiyavong
authors.forename: L
authors.initials: L
authors.lastname: Lloyd
authors.forename: A M
authors.initials: AM
authors.lastname: McGregor
mesh_terms: D000483:Alleles; D015139:Blotting, Southern; D002872:Chromosome Deletion; D003181:Complement C4 / Q000235:genetics*; D015934:Complement C4a; D005260:Female; D005838:Genotype; D006111:Graves Disease / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D015795:HLA-B8 Antigen; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D015183:Restriction Mapping
chemical_list: D003181:Complement C4; D015235:HLA-B Antigens; D015795:HLA-B8 Antigen; D006684:HLA-DR Antigens; D015934:Complement C4a