C4 Genotype

Immunology

---

Description

In peripheral blood plasma, total C4 protein levels can vary across the population, with most individuals falling within the normal reference range of 0.14 to 0.54 g/L. This high degree of variability is due to multiple contributing factors, including the individuals physiological state, C4 gene copy numbers, and intrinsic polymorphisms in cis-acting DNA elements that may alter C4 expression. Low complement component C4 levels can occur due to consumption through activation of the complement pathway, or alternatively can occur due to deficiency. Currently total C4 is measured, however intrinsic genetic mechanisms result in the production of differing quantities of C4A and C4B proteins in individuals, causing instances of partial or complete deficiency. Across the population this creates a wide amount of variation, including complete absence of C4A or C4B, more C4A than C4B, more C4B than C4A, or equal quantities of both [1]. The overall gene copy numbers of total C4, C4A, or C4B may causes differences in susceptibilities to autoimmune or infectious disease. Genetic studies in the form of allotyping and measuring gene copy number can be used to determine if low C4 levels are due to genetic factors or complement consumption. This can be of use to some specialities such as Rheumatology that may use C4 levels to monitor disease activity.

---

Indications

Instances of persistently, unexplained low C4 quantitation.

---

Sample Type

Serum (Gel 5mL Yellow) or EDTA.
Requests from outside Sheffield: transport at ambient temperature via Royal Mail or Courier.

---

Reference Range

Normal is no deletion in copy number.

---

Turnaround Time

Within 4 weeks

---

Testing Frequency

As required

---

References

Rebmann, Y., Doxiadis, I., Kubens, B.S., Grosse-Wilde, H. Quantitation of the human component C4: definition of C4 Q0 alleles and C4A duplications. Vox Sang. 1992. 62:117-123. [Ref 1].
Wu, Y.L., Yang, Y., Chung, E.K., et al. Phenotypes, genotypes and disease susceptibility associated with gene copy number variations: complement C4 CNVs in European American healthy subjects and those with systemic lupus erythematosus. Cytogenet Genome Res. 2009. 123: 131-141.
Mayilyan, K.R. Complement genetics, deficiencies and disease associations. Protein Cell. 2012. 3:487-96.
Yang, Y., Erwin, K., Chung, Y.L. Gene Copy-Number Variation and Associated Polymorphisms of Complement Component C4 in Human Systemic Lupus Erythematosus (SLE): Low Copy Number Is a Risk Factor for and High Copy Number Is a Protective Factor against SLE Susceptibility in European Americans. American Journ Hum Gen. 2007. 80:1037-1054.

---

See Also

C4
C3

Please note: the above information is subject to change and we endeavour to keep this website up to date wherever necessary.