Complement Component 4A

Alternative Names

  • C4A
  • Complement Component 4S
  • C4S
  • Acidic C4
  • Rodgers Form of C4
  • Complement Component 4A Deficiency
  • Rodgers Blood Group
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OMIM Number

120810

Gene Map Locus
6p21.3

Description

The complement component 4A (C4A) is a protein factor, which is part of the complement system, a cascade of serum proteins that play a role in the development of inflammatory reactions. C4 is capable of inducing vasodilatation, increasing capillary permeability, increase expression of leukocyte adhesion molecules, and promote phagocyte chemotaxis.

Along with C3, C4 levels in the serum and other body fluids are also used in the identification of several disease states. Increased C4 levels are seen in conditions such as cancer, rheumatoid arthritis, and ulcerative colitis, whereas reduced levels are observed in systemic lupus erythematosus, type I diabetes mellitus, bacterial infections, cirrhosis, hepatitis, and rejection of kidney transplants.

Molecular Genetics

The C4A gene is located on chromosome 6p, within the class III MHC region, where it spans a length of 20Kb of DNA. The gene shows strong similarity to the C3 gene. It consists of 41 exons, which code for a protein consisting of 1744 amino acids. Individuals may carry up to three copies of this gene. The protein is initially expressed in the form of a single chain precursor, which is then cleaved into a trimer of alpha, beta, and gamma chains and then gets secreted. The alpha chain is later cleaved into C4a and C4B fragments. C4B remains linked to the beta and gamma chains, whereas C4a functions as an anaphylotoxin.

Epidemiology in the Arab World

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Other Reports

Oman

White et al. (1997) measured the levels of C3 and C4 in 100 healthy Omani adults (50 males and 50 females) to obtain local reference values (which were compared to those of other populations) to be used when evaluating patients from the same population. The subjects were university students, blood donors, and healthy potential bone marrow and kidney donors and were not related to each other. The complement levels were measured by nephelometry, and the results were analyzed statistically. The mean of C4 level was found to be 1.57 SD 0.52 micro-mol/L (min value of 0.71, max value of 3.07) with 95% confidence interval of 1.46 - 1.67. These values were not different between males and females, and they were not different from those reported from other Western populations.

Tunisia

Jenhani et al. (1992) investigated the polymorphism of C4A and C4B genes in Tunisian patients with insulin dependent diabetes (IDDM) and compared to family members (sibs) and to healthy controls. A significant increase in C4AQO (26.86% vs 6.90%) and C4BQO (40.29% vs 8.28%) phenotypes was noted in IDDM patients compared with controls. Using RFLP analysis, a high frequency of C4 null alleles was confirmed and most of their genes were deleted in IDDM patients (72.23% vs 20% for CA4QO and 74.07% vs 16.70% for C4BQO). A significant decrease in the C4B long (14.92% vs 67.12%) form of the gene was also demonstrated by RFLP analysis compared with controls.

In 2004, Ayed et al. compared HLA-DRB1*, DQA1, DQB1* and C4 allotypes in 62 Tunisian patients with systemic lupus erythematosus and 100 matched controls. HLA-DRB1*0301, -DRB1*1501 and C4AQO alleles were increased in the SLE patients, while the frequencies of HLA-DRB1*04 and DQB1*03 were decreased. C4A*QO and C4B*QO were increased in frequency in the SLE patients compared to the controls, but only C4A null was significantly increased. Eleven of 17 SLE patients with the C4 null allele were HLA-DRB1*0301 positive.

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