Serum phospholipids are the main environmental determinants of activated factor VII in the most common FVII genotype. European Union Concerted Action "Clotart".
OBJECTIVE
Numerous studies have emphasized the role of triglyceride-rich lipoproteins and of Factor VII (FVII) polymorphisms in determining levels of FVII activity.


METHODS
This study was undertaken to evaluate the role of other lipid fractions and the interaction between lipids and FVII in subjects with recognised genotypes. Volunteer subjects (n=459) from 5 European countries were studied. Blood samples were drawn irrespective of the time of day or fasting status. Levels of FVII activity (FVIIc), activated FVII (FVIIa) and FVII antigen (FVIIAg) were evaluated with reference to a number of lipid parameters (HDL-, LDL- and total cholesterol, triglycerides, phospholipids, lipoprotein(a), and apoliproptein A1). The two most common FVII polymorphisms were analyzed in combination (353R/Q and 5'F7; alleles M1/M2 and A1/A2, respectively).


RESULTS
Homozygotes for the A1 and M1 alleles (M11/A11) had significantly higher FVII levels. At multiple regression analysis the strongest predictor of FVIIa and FVIIc was the concentration of phospholipids. This interaction was confined to the A11M11 genotype subjects.


CONCLUSIONS
These data indicate that lipids contribute mainly to FVIIa levels through their phospholipid content, and that the degree of this contribution is strictly dependent on FVII genotypes.
Mariani
G
G
Hematology and BMT Unit, University Hospital, via del Vespro 129, 90127 Palermo, Italy. mariangu@tin.it
Bernardi
F
F
Bertina
R
R
Vicente
V V
VV
Prydz
H
H
Samama
M
M
Sandset
P M
PM
Di Nucci
G D
GD
Testa
M G
MG
Bendz
B
B
Chiarotti
F
F
Ciarla
M V
MV
Strom
R
R
D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D005167:Factor VII / Q000235:genetics* / Q000378:metabolism; D015942:Factor VIIa / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood*; D011110:Polymorphism, Genetic; D012737:Sex Factors
D010743:Phospholipids; D005167:Factor VII; D015942:Factor VIIa