The relationship between FCN2 genotypes and serum ficolin-2 (L-ficolin) protein concentrations from a large cohort of neonates

The human FCN2 gene codes for ficolin-2 (L-ficolin), a major pattern recognition molecule and activator of the lectin pathway of complement. Seven single nucleotide polymorphisms of this gene were investigated in a large series of cord blood DNA samples. Mutations from the majority to the minority alleles at −602, −4 and +6359 were associated with an increase, while mutations at −986, −557, −64 and +6424 were associated with a decrease, in protein concentration. Full (7 loci) genotypes were obtained for 1229 unrelated neonates, 12 sets of twin siblings and one set of triplets. Forty-four separate genotypes were detected. Four genotypes accounted for more than half the unrelated neonates, and >90% had one of the 12 commonest genotypes. Genotypes were associated with significant differences in mean serum ficolin-2, but the intra-genotype concentration ranges were large and greater than the inter-genotype differences. Consequently, there were no associations between genotypes and low birthweight babies or perinatal infections, and only a weak relationship with preterm deliveries, despite all three adverse pregnancy features being significantly associated with serum ficolin-2 protein. FCN2 genotyping may be of value in clinical studies, but not as a substitute for total serum ficolin-2 protein measurement.