Genetic and environmental factors influencing the human factor H plasma levels.
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.
Esparza-Gordillo
Jorge
J
Departamento de Inmunología, Laboratorio 143, Centro de Investigaciones Biológicas (CSIC), C/ Ramiro de Maeztu N masculine 9, 28040, Madrid, Spain.
Soria
José Manuel
JM
Buil
Alfonso
A
Almasy
Laura
L
Blangero
John
J
Fontcuberta
Jordi
J
Rodríguez de Córdoba
Santiago
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D019655:Quantitative Trait, Heritable
C493495:CFH protein, human; D017242:Complement Factor H