Complement Component 1qA (C1qa)

Complement Component C1Q: C1QA Background

Complement component C1q is the trigger activation of the complement cascade in the presence of immune complexes, it's formed by six trimers of A, B and C chains. The C1qA gene, located on chromosome 1p36.3-p34.1, contains several single nucleotide variations that are currently catalogued in the NCBI database. Complement component C1qA is located at the beginning of the second exon. Two of these are located in the intron and three in the 3′ untranslated region of the gene. The only coding single nucleotide polymorphism (SNP) is C1qA[276A/G] (rs172378) and is located at the beginning of the second exon.

An absolute correlation between complete serum C1q deficit and homozygous C1qA[276A] genotype in patients from seven families with different forms of C1q deficiencies has been reported. The finding that a deficiency in complement is associated with enhanced autoimmunity would seem to be counterintuitive. One possible explanation is that complement deficiency results in impaired clearance of apoptotic cells or cellular debris, and this leads to an enhanced autoimmune response. Indeed, complement component C1q has been shown to play a critical role in the clearance of apoptotic bodies and limitation of autoimmunity. Based on these observations, it is conceivable that a weaker complement system might be less effective against circulating microorganisms but, at the same time, lead to a more rigorous cellular immune response. Thus, paradoxically, decreased complement activity could lead to enhanced cellular immunity to intracellular organisms or malignancy.

Hundreds of SNPs suspected to either predispose to cancer or alter clinical outcome have been studied. Given that complement may play a role in clearing tumor cells, either alive or dead, and polymorphisms in complement component C1qA may change the functionality of the complement system, we evaluated whether polymorphism in the C1qA locus correlate with the development of sites of metastasis in breast cancer associated with hematogenous spreading of disease.

Complement Component C1Q: C1QA Reference

1. Racila E, et al. (2006). The pattern of clinical breast cancer metastasis correlates with a single nucleotide polymorphism in the C1qA component of complement. Immunogenetics, 58(1), 1-8.
2. Tong H H, et al. (2010). Enhanced susceptibility to acute pneumococcal otitis media in mice deficient in complement C1qa, factor B, and factor B/C2. Infection and immunity, 78(3), 976-983.
3. Wang Y, et al. (2012). The complement C1qA enhances retinoic acid‐inducible gene‐I‐mediated immune signalling. Immunology, 136(1), 78-85.