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Inherited structural and quantitative polymorphisms of C3b receptor (CR1) in normals and patients with glomerular
G Panchamoorthy1, S C Tiwari, L M Srivastava
1Department of Biochemistry and Nephrology, All India Institute of Medical Sciences, New Delhi.
Insights
Erythrocyte complement receptor 1 (CR1) exhibits structural and quantitative polymorphisms in Indians. These CR1 variations do not correlate with susceptibility to glomerular diseases.
Area of Science:
- Immunogenetics
- Nephrology
Background:
- Erythrocyte complement receptor 1 (CR1) plays a role in immune complex clearance.
- Polymorphisms in CR1 structure and quantity are known but their association with glomerular diseases requires further investigation.
Purpose of the Study:
- To investigate structural and quantitative polymorphisms of erythrocyte CR1 in normal Indian individuals and patients with glomerular diseases.
- To determine if CR1 polymorphisms are associated with susceptibility to glomerular diseases.
Main Methods:
- Purification of CR1 using immunoprecipitation or C3b-Sepharose affinity chromatography.
- Electrophoresis to identify structural polymorphic patterns (190 kDa and 220 kDa).
- Evaluation of CR1 levels to assess quantitative expression (L and H alleles).
Main Results:
- Two structural CR1 polymorphic patterns (190 kDa and 220 kDa) with gene frequencies of 0.975 and 0.025 were identified in normal Indians, unaltered in patients.
- A trimodal distribution of CR1 levels suggested co-dominant alleles (L and H) with frequencies of 0.523 and 0.477.
- Structural and quantitative CR1 alleles are not linked, and no functional differences were observed among structural forms.
Conclusions:
- CR1 structural and quantitative polymorphisms in Indians are not associated with susceptibility to glomerular diseases.
- Observed decrease in CR1 levels in patients with acute glomerulonephritis is likely an acquired characteristic.
- No functional differences among CR1 polymorphic forms suggest they do not influence glomerular disease risk.
Abstract:
The erythrocyte C3b receptor (CR1) has been studied for its structural and quantitative polymorphisms in normal Indian individuals and in patients with glomerular diseases. In the normal Indian population, purification of CR1 by immunoprecipitation or C3b-Sepharose affinity column and subjecting it to electrophoresis showed the existence of two types of structural polymorphic patterns with M(r) of 190 kDa and 220 kDa, and with gene frequencies of 0.975 and 0.025, respectively. The gene frequencies of these alleles remain unaltered in the patient population. Evaluation of CR1 levels in the normal Indian population revealed a trimodal distribution of CR1 number suggesting a co-dominant allelic pattern (L and H alleles) for the quantitative expression of CR1 with gene frequencies of 0.523 and 0.477, respectively. In our earlier study we have shown that there is a decreased expression of CR1 on the erythrocytes of patients with acute glomerulonephritis. Since this decrease in the CR1 level in patients is an acquired characteristic, it may not be the level controlled by the LL homozygous alleles. The discrepancy in the gene frequencies of the structural and quantitative polymorphic alleles in normal individuals show that they are not linked to each other. In our earlier study, we showed that the affinity constant of C3b-CR1 binding in different individuals remains the same irrespective of the number of CR1 on the erythrocyte surface. Comparison of this result with the present investigation shows that there is no functional difference among various structural polymorphic forms of CR1 and the susceptibility to glomerular diseases is not associated with any of the CR1 polymorphic patterns.