Genetic and structural polymorphism of complement receptor 1 in normal Indian subjects.

Area of Science:

• Immunogenetics
• Human Genetics
• Molecular Biology

Background:

• Complement receptor 1 (CR1), also known as CD35, is a polymorphic glycoprotein expressed on various immune cells and kidney podocytes.
• CR1 exists in soluble (sCR1) and urinary (uCR1) forms, with known structural and genomic polymorphisms influencing health and disease.
• Previous studies have examined CR1 polymorphisms separately, lacking simultaneous investigation in the same cohort.

Purpose of the Study:

• To conduct the first simultaneous study of structural and genomic polymorphism of CR1 in a healthy Indian population.
• To analyze the distribution of CR1 phenotypes and gene frequencies.
• To assess the genetic model underlying CR1 polymorphism in the studied population.

Main Methods:

• Recruitment of 101 healthy Indian volunteers through random sampling.
• Analysis of both quantitative (erythrocyte CR1 expression levels: HH, HL, LL) and structural (CR1 protein size: A, B, C, D) CR1 polymorphisms.
• Application of Hardy-Weinberg equilibrium to evaluate the genetic model.

Main Results:

• Identified AA phenotype in 84.2%, AB in 14.8%, and a novel BB phenotype (0.9%) in Indian subjects.
• Determined relative gene frequencies for structural alleles (A: 0.916, B: 0.084) and quantitative alleles (H: 0.51, L: 0.49).
• Observed higher frequencies of HL (54.45%) and AA phenotypes, with findings aligning with Hardy-Weinberg equilibrium, suggesting autosomal co-dominant inheritance.

Conclusions:

• CR1 structural and quantitative polymorphisms are encoded by autosomal co-dominant alleles.
• The study reports the first instance of the homozygous BB phenotype in Indian subjects.
• CR1 gene frequencies in this Indian cohort represent a unique combination of those observed in Caucasian and Oriental populations.