TY - JOUR
T1 - Genetic polymorphisms modify the response of factor VII to oral contraceptive use
T2 - An example of gene-environment interaction
AU - Bloemenkamp, Kitty W.M.
AU - De Maat, Moniek P.M.
AU - Dersjant-Roorda, Marianne C.
AU - Helmerhorst, Frans M.
AU - Kluft, Cornelis
PY - 2002/8/1
Y1 - 2002/8/1
N2 - Elevated plasma levels of factor VII and fibrinogen are risk factors for cardiovascular disease, especially arterial thrombosis. Oral contraceptive use increases factor VII and fibrinogen plasma levels. It has been described that DNA polymorphisms are associated with the plasma levels of hemostatic variables and their regulation. The R/Q353 polymorphism in the factor VII gene and the -455G/A polymorphism in the fibrinogen β-gene are associated with plasma levels of factor VII and fibrinogen, respectively. We analysed data of a randomised study (n=95) in which two types of oral contraceptives were compared with regard to their effect on factor VII and fibrinogen, in which we also determined R/Q353 and -455G/A polymorphisms. Women were allocated randomly to either receiving a monophasic oral contraceptive containing 75 μg of gestodene and 20 μg of ethinyl estradiol, or 150 μg of desogestrel and 20 μg of ethinyl estradiol. Blood was taken before treatment and after 3 and 6 months of oral contraceptive use. Factor VII and fibrinogen increased significantly after 3 and 6 months of oral contraceptive use; the increase in factor VII was higher in the desogestrel group than in the gestodene group at 3 and 6 months. For fibrinogen, there were no intergroup differences at 3 and 6 months. At baseline, an association between genotype and plasma factor VII and fibrinogen levels was observed. In multivariate analysis, the R/Q353 polymorphism and the type of oral contraceptive were determinants of the effect on the change in factor VII, with the highest increase in women carrying the Q allele and using the desogestrel-containing oral contraceptive, and the lowest increase in women with the RR genotype who use the gestodene-containing oral contraceptive. For fibrinogen, no interaction among type of oral contraceptive, -455G/A polymorphism, and change in plasma levels was observed. We conclude that an individual's genetic variation may contribute to the response of plasma factor VII to oral contraceptive use.
AB - Elevated plasma levels of factor VII and fibrinogen are risk factors for cardiovascular disease, especially arterial thrombosis. Oral contraceptive use increases factor VII and fibrinogen plasma levels. It has been described that DNA polymorphisms are associated with the plasma levels of hemostatic variables and their regulation. The R/Q353 polymorphism in the factor VII gene and the -455G/A polymorphism in the fibrinogen β-gene are associated with plasma levels of factor VII and fibrinogen, respectively. We analysed data of a randomised study (n=95) in which two types of oral contraceptives were compared with regard to their effect on factor VII and fibrinogen, in which we also determined R/Q353 and -455G/A polymorphisms. Women were allocated randomly to either receiving a monophasic oral contraceptive containing 75 μg of gestodene and 20 μg of ethinyl estradiol, or 150 μg of desogestrel and 20 μg of ethinyl estradiol. Blood was taken before treatment and after 3 and 6 months of oral contraceptive use. Factor VII and fibrinogen increased significantly after 3 and 6 months of oral contraceptive use; the increase in factor VII was higher in the desogestrel group than in the gestodene group at 3 and 6 months. For fibrinogen, there were no intergroup differences at 3 and 6 months. At baseline, an association between genotype and plasma factor VII and fibrinogen levels was observed. In multivariate analysis, the R/Q353 polymorphism and the type of oral contraceptive were determinants of the effect on the change in factor VII, with the highest increase in women carrying the Q allele and using the desogestrel-containing oral contraceptive, and the lowest increase in women with the RR genotype who use the gestodene-containing oral contraceptive. For fibrinogen, no interaction among type of oral contraceptive, -455G/A polymorphism, and change in plasma levels was observed. We conclude that an individual's genetic variation may contribute to the response of plasma factor VII to oral contraceptive use.
KW - Factor VII
KW - Genetic polymorphisms
KW - Oral contraceptive
UR - http://www.scopus.com/inward/record.url?scp=0345701535&partnerID=8YFLogxK
U2 - 10.1016/S1537-1891(02)00300-2
DO - 10.1016/S1537-1891(02)00300-2
M3 - Article
C2 - 12616980
AN - SCOPUS:0345701535
SN - 1537-1891
VL - 39
SP - 131
EP - 136
JO - Vascular Pharmacology
JF - Vascular Pharmacology
IS - 3
ER -