Common haplotypes within the chromosome 1q31.3 region determine systemic concentrations of the entire complement factor H protein family.

The alternative pathway (AP) of complement activation is consistently active, keeping the complement system primed for immediate response. This constant "tick-over" mechanism is regulated by the factor H (FH) protein family, which encompasses seven highly related proteins: FH, FHL-1, and five FH-related (FHR-1 to -5) proteins. The current model is that FHR proteins compete with FH and FHL-1 to fine-tune their activities, though their exact role remains unclear. Genetic studies of this complex locus and measurement of individual protein members have revealed distinct haplotypes associating with a wide range of human diseases; highlighting the significant role of this protein family in complement regulation. However, a full assessment of systemic protein concentration of the complete FH protein family, accounting for the known genetic heterogeneity within populations, is still lacking. In this report, utilizing specific FH protein family ELISAs, we demonstrate the impact of common haplotypes within the chromosome 1q31.3 region on the relative abundance of all FH protein family members. These common haplotypes give rise to classifiable protein expression patterns, establishing distinct ratios between FH, FHL-1 and the FHRs. The obtained reference intervals and genetic determinants supports further investigations into this protein family in both health and disease and serves as a benchmark for future studies.