Coagulation factor VII, R353Q polymorphism, and serum choline-containing phospholipids in males at high risk for coronary heart disease.
BACKGROUND
Elevated levels of coagulation factor VII (FVII) have been associated with increased risk for myocardial infarction (MI). The R353Q polymorphism of the FVII gene has been shown to modify plasma levels of FVII, and has in some studies also been associated with reduced risk for MI.


OBJECTIVE
To examine the R353Q polymorphism of the FVII gene and the relation to myocardial infarction (MI), cardiovascular disease (CVD), and diabetes, and furthermore, to elucidate the association between the polymorphism and plasma levels of FVII coagulant activity (FVIIc), FVII antigen (FVIIag), activated FVII (FVIIa), and serum choline-containing phospholipids (PC).


METHODS
In 560 elderly men characterised as hypercholesterolemic in 1972, we examined the R353Q polymorphism by melting curve analysis after real-time PCR. In a subgroup of 205 individuals, FVIIc, FVIIag, FVIIa, and PC were analysed.


RESULTS
There were no significant associations between genotype and the disease states, although we observed a lower number of MI cases among subjects with the Q allele, compared to the RR individuals (14% vs. 19%). FVIIag and FVIIc levels were lower in RQ compared to RR subjects, whereas for FVIIa the opposite was observed (p<0.001 for all). PC correlated positively with FVIIag (r=0.24, p<0.001), but negatively with FVIIa (r=-0.25, p<0.001). No genotype specific interactions were found for the association between FVII and PC.


CONCLUSIONS
No significant associations between the R353Q polymorphism and MI, CVD, or diabetes were observed, although the polymorphism strongly influenced plasma levels of FVII. Serum PC correlated significantly with FVIIag and inversely with FVIIa, independently of genotype.
Lindman
Anja S
AS
Center for Clinical Research, Ullevål University Hospital, Oslo, Norway. anja1@basalmed.uio.no
Pedersen
Jan I
JI
Arnesen
Harald
H
Hjerkinn
Elsa M
EM
Veierød
Marit B
MB
Prydz
Hans
H
Seljeflot
Ingebjørg
I
D000368:Aged; D002794:Choline / Q000097:blood*; D015897:Comorbidity; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology*; D003920:Diabetes Mellitus / Q000097:blood / Q000453:epidemiology; D005167:Factor VII / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology / Q000235:genetics; D008297:Male; D015999:Multivariate Analysis; D009664:Norway / Q000453:epidemiology; D010743:Phospholipids / Q000032:analysis / Q000097:blood*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors
D010743:Phospholipids; D005167:Factor VII; D002794:Choline