Plasma factor VII levels are influenced by a polymorphism in the promoter region of the FVII gene.
Genetic factors play a role in determining the variability of plasma factor VII (FVII) levels in healthy individuals. There is also evidence that high serum lipids are associated with high FVII levels in plasma. In the promoter region of the human FVII a DNA polymorphism has been described, originating from a decanucleotide insert present in the less frequent allele. This biallelic system, reflecting the absence (AA) or presence (Aa) of the decanucleotide, can be detected by a DNA enzyme immunoassay of PCR products. We evaluated the association between the polymorphic alleles and the levels of FVII:Ag and FVII:C in 100 healthy individuals and in 19 hypertriglyceridemic individuals. Among healthy individuals, mean FVII:Ag and FVII:C levels of those with the homozygous genotype (A/A; mean FVII:Ag 112%, mean FVII:C 109%) were significantly higher (P < 0.001) than the mean levels of those with the heterozygous genotype (A/a, mean FVII:Ag 80%, mean FVII:C 90%; P < 0.001). Similar genotype-associated differences for FVII:Ag and FVII:C were found in individuals with triglycerides above 250 mg/dl (P < 0.05). FVII:C and FVII:Ag levels were positively related to triglycerides only in individuals without the insert (P < 0.01); there was no significant relationship in those carrying the allele with the insert (A/a; P = 0.43 and 0.08). Our findings of genotype-associated differences in FVII levels and interactions with triglycerides are similar to those obtained with the amino acid dimorphism at position 353 of the factor VII protein.
Sacchi
E
E
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Milan, Italy.
Tagliabue
L
L
Scoglio
R
R
Baroncini
C
C
Coppola
R
R
Bernardi
F
F
Mannucci
P M
PM
D000328:Adult; D000941:Antigens / Q000032:analysis; D005167:Factor VII / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012044:Regression Analysis
D000941:Antigens; C042580:factor VII clotting antigen; D005167:Factor VII