TY - JOUR
T1 - The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin system in determining plasma t-PA and PAI-I levels
AU - Asselbergs, Folkert W.
AU - Williams, Scott M.
AU - Hebert, Patricia R.
AU - Coffey, Christopher S.
AU - Hillege, Hans L.
AU - Navis, Gerjan
AU - Vaughan, Douglas E.
AU - van Gilst, Wiek H.
AU - Moore, Jason H.
PY - 2006/10
Y1 - 2006/10
N2 - Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor I (PAI-I) directly influence thrombus formation and degradation and thus risk for arterial thrombosis. We report here results from a genetic analysis of plasma t-PA and PAI-I levels in a large population-based sample from the PREVEND study in Groningen, the Netherlands (n=2,527). We measured polymorphisms from genes of the fibrinolytic system, the renin-angiotensin system (RAS), and the bradykinin system. We found that males had higher levels of natural-log transformed t-PA, and PAI- I (P < 0.01) compared to females. When stratifying females by menopausal status, PAI-I levels were only significantly different between pre-menopausal females and males (p<0.001). Furthermore, we found that age, body mass index, and waist-to-hip ratio were significant predictors of t-PA and PAI-I in both females and males, and that the regression relationships between these factors and plasma t-PA and PAI-I were dependent on gender. In addition, we found that the PAI-I 4G/5G polymorphism was a significant predictor of PAI-I levels in both females and males, that the angiotensin II type 1 receptor A1166C was a significant predictor of t-PA and PAI-I levels in females, and that the brodykinin receptor B2 58CT polymorphism was a significant predictor of t-PA levels in females. In conclusion, this large population-based study showed that t-PA and PAI-I levels are determined by several demographic and genetic factors involved in the fibrinolytic, RAS and bradykinin system. In addition, the results support the idea that the biology of t-PA and PAI-I is different between females and males. © 2006 Schattauer GmbH, Stuttgart.
AB - Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor I (PAI-I) directly influence thrombus formation and degradation and thus risk for arterial thrombosis. We report here results from a genetic analysis of plasma t-PA and PAI-I levels in a large population-based sample from the PREVEND study in Groningen, the Netherlands (n=2,527). We measured polymorphisms from genes of the fibrinolytic system, the renin-angiotensin system (RAS), and the bradykinin system. We found that males had higher levels of natural-log transformed t-PA, and PAI- I (P < 0.01) compared to females. When stratifying females by menopausal status, PAI-I levels were only significantly different between pre-menopausal females and males (p<0.001). Furthermore, we found that age, body mass index, and waist-to-hip ratio were significant predictors of t-PA and PAI-I in both females and males, and that the regression relationships between these factors and plasma t-PA and PAI-I were dependent on gender. In addition, we found that the PAI-I 4G/5G polymorphism was a significant predictor of PAI-I levels in both females and males, that the angiotensin II type 1 receptor A1166C was a significant predictor of t-PA and PAI-I levels in females, and that the brodykinin receptor B2 58CT polymorphism was a significant predictor of t-PA levels in females. In conclusion, this large population-based study showed that t-PA and PAI-I levels are determined by several demographic and genetic factors involved in the fibrinolytic, RAS and bradykinin system. In addition, the results support the idea that the biology of t-PA and PAI-I is different between females and males. © 2006 Schattauer GmbH, Stuttgart.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33749865720&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/17003924
U2 - https://doi.org/10.1160/TH06-06-0335
DO - https://doi.org/10.1160/TH06-06-0335
M3 - Article
C2 - 17003924
SN - 0340-6245
VL - 96
SP - 471
EP - 477
JO - Thrombosis and haemostasis
JF - Thrombosis and haemostasis
IS - 4
ER -