Related Experiment Videos
CR1 polymorphism in hydralazine-induced systemic lupus erythematosus: DNA restriction fragment length polymorphism
1Department of Pharmacology, University of Oxford, England.
Insights
Genetic factors do not predispose individuals to hydralazine-induced systemic lupus erythematosus (SLE). However, genetically
Area of Science:
- Immunogenetics
- Rheumatology
- Pharmacogenomics
Background:
- Hydralazine (Hz) therapy can induce systemic lupus erythematosus (SLE).
- Reduced erythrocyte complement receptor 1 (CR1) levels are observed in Hz-induced SLE.
- The genetic contribution to these reduced CR1 levels is not fully understood.
Purpose of the Study:
- To investigate the role of genetic factors in erythrocyte CR1 expression.
- To determine if specific CR1 gene polymorphisms are associated with hydralazine-induced SLE.
Main Methods:
- Analysis of a HindIII restriction fragment length polymorphism (RFLP) in the CR1 gene.
- Comparison of allele frequencies in Hz-SLE patients, Hz-treated controls, and their relatives.
- Quantification of erythrocyte CR1 levels in different genetic subgroups.
Main Results:
- No significant difference in CR1 gene allele frequencies between Hz-SLE patients and controls.
- Hz-SLE patients homozygous for the 'high expressor' allele had lower mean erythrocyte CR1 levels.
- Low CR1 levels in 'high expressor' Hz-SLE patients correlated with elevated circulating immune complexes.
Conclusions:
- Genetic predisposition to low erythrocyte CR1 expression does not appear to cause Hz-induced SLE.
- In genetically 'high expressor' individuals, reduced CR1 levels may be linked to immune complex formation in Hz-SLE.
Abstract:
The contribution of genetic factors in the reduction in erythrocyte CR1 levels observed in hydralazine (Hz) induced systemic lupus erythematosus (SLE) was investigated by determining the frequency of a HindIII restriction fragment length polymorphism (RFLP) in the CR1 gene. This RFLP is associated with quantitative erythrocyte CR1 expression. Individuals who have developed SLE as a reaction to Hz therapy, consanguinous relatives of the Hz-SLE patients, controls who had been treated with Hz without any adverse reaction, and the consanguinous relatives of these controls were included in this study. No difference was found in the frequency of occurrence of the alleles associated with CR1 expression between the Hz-SLE patients and the control groups (P greater than 0.2). Individuals from the Hz-SLE group who were homozygous for the 7.4 kb 'high expressor' allele had lower mean levels of erythrocytes CR1 (564 +/- 65) than the corresponding homozygous subgroups within the Hz-SLE relative group (774 +/- 46), the Hz control group (756 +/- 80) and the Hz control relatives group (825 +/- 66). In addition, 50% of the Hz-SLE patients in the 'high expressor' subgroup who had less than 500 CR1 per erythrocyte had elevated levels of circulating immune complexes. This study suggests that individuals who are genetically low expressors of erythrocyte CR1 are not predisposed to developing SLE in response to Hz therapy, and that in a subgroup of genetically 'high expressors', low CR1 levels are associated with elevated levels of circulatory immune complexes.