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C4A gene deletion: association with Graves' disease
S Ratanachaiyavong1, L Lloyd, A M McGregor
1Department of Medicine, King's College Hospital Medical School, Denmark Hill, London.
Journal of Molecular Endocrinology
|September 1, 1989
Summary
The non-expressed C4A allele (C4A*Q0) is strongly associated with Graves' disease, particularly when linked with HLA-B8 and/or DR3. This finding improves understanding of autoimmune disease genetics.
Area of Science:
- Immunogenetics
- Autoimmune Diseases
Background:
- Human Leukocyte Antigen (HLA) antigens, especially HLA-B8 and DR3, are linked to autoimmune disorders.
- The C4A*Q0 allele, often in linkage disequilibrium with HLA-B8,DR3, has been implicated in Graves' disease but its assignment was challenging.
Purpose of the Study:
- To resolve the assignment of the C4A*Q0 allele using phenotypic and genotypic methods.
- To determine the significance of the C4A*Q0 allele in Graves' disease patients and healthy controls.
Main Methods:
- Phenotypic and genotypic analysis of C4A*Q0 allele in 80 Graves' disease patients and 50 controls.
- Utilized C4 cDNA probe for C4A gene deletion analysis.
- Employed C4 DNA analysis with TaqI or EcoRI restriction enzymes.
Main Results:
- A significant association was found between C4A*Q0 allele and Graves' disease (56% vs 26%, P<0.002).
- The association was stronger with HLA-B8 and/or DR3 (92% vs 70.6%, P<0.04).
- C4A*Q0 alleles linked to HLA-B8/DR3 were due to C4A gene deletion, detectable by DNA analysis.
Conclusions:
- The C4A*Q0 allele is strongly associated with Graves' disease, especially in individuals with HLA-B8 and/or DR3.
- C4A gene deletion is the cause of C4A*Q0 in these cases.
- Combined C4 protein typing and DNA analysis offers the best method for C4A*Q0 determination in unrelated individuals.