Gc-globulin concentrations and C5 haplotype-tagging polymorphisms contribute to variations in serum activity of complement factor C5

Objectives: To investigate the role of Gc-globulin and C5 gene variants as co-factors in the regulation of profibrogenic C5 serum activities. Design: Retrospective clinical investigation with 100 healthy probands. Genomic DNA was isolated from whole blood and examined for the human C5 htSNPs rs17611 and rs2300929. Actin-free Gc-globulin-, total Gc-globulin- and total C5-concentrations in serum were measured using ELISA assays; C5 activities in serum were determined using radial immunodiffusion. Results: C5 serum concentrations were significantly elevated in individuals carrying at least one profibrogenic allele of the C5 htSNP rs17611, but no association between C5 htSNPs and C5 serum activities was detected, albeit C5 activities correlated positively with C5 concentrations in serum. However, C5 activities were also positively correlated with total and actin-free Gc-globulin concentrations. Conclusion: Our findings indicate that C5 gene variants and Gc-globulin levels co-define the proinflammatory and profibrogenic effects of C5 in patients at-risk for progression of liver fibrosis.