Genetic and environmental factors influencing the human factor H plasma levels

Immunogenetics. 2004 May;56(2):77-82. doi: 10.1007/s00251-004-0660-7. Epub 2004 Apr 30.


Factor H is a plasma protein that plays a critical role in the regulation of complement activation in fluid phase and on cellular surfaces. Over the years numerous reports have illustrated the association of factor H deficiencies with chronic renal and infectious diseases. Plasma levels of factor H show a five-fold range of variation in humans (116-562 microg/ml), which may also be relevant to disease susceptibility. To quantify the effects of the genetic and environmental factors responsible for the variation in the factor H plasma levels, we have applied variance-component methods to a family-based sample. Factor H plasma levels show an age-dependent increase ( P<0.0001) and are decreased in smokers ( P<0.0001). Interestingly, the heritability of the factor H trait is very high ( h(2)=0.62+/-0.07; P<0.0001), indicating that 62% of the factor H phenotypic variance is due to the additive effects of genes. On this premise, we conducted a genome-wide linkage screen in order to identify genes regulating the factor H trait. Three genomic regions (1q32, 2p21-24 and 15q22-24) provided suggestive evidence of linkage (LOD scores 2.03, 2.15 and 2.00, respectively) with the plasma levels of factor H.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 15 / genetics
  • Chromosomes, Human, Pair 2 / genetics
  • Complement Factor H / genetics*
  • Complement Factor H / metabolism*
  • Female
  • Genetic Linkage*
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Infant
  • Infant, Newborn
  • Lod Score
  • Male
  • Middle Aged
  • Quantitative Trait, Heritable*


  • CFH protein, human
  • Complement Factor H