[Plasminogen activator inhibitor-1 (PAI-1) 4G/5G and angiotensin converting enzyme (ACE) I/D gene polymorphisms and fibrinolytic activity in patients with essential hypertension and dyslipidemia].
Essential arterial hypertension often predisposes patients to prothrombotic state and increased risk of vascular and organ complications. Vital role in regulation of hemostatic processes is played by genetic factors, renin-angiotensin system and disorders of lipid metabolism. Prime genetic factors involved in the process are 4G/5G polymorphism of promoter region coding tissue plasminogen activator inhibitor-1 (PAI-1) and I/D polymorphism for angiotensin converting enzyme (ACE) gene. The aim of work was the evaluation of alterations within fibrinolysis system (estimation of t-PA and PAI-1 levels), fibrinogen concentration (Fb) and ACE activity with regard to co-existent dyslipidemia and features of left ventricle hypertrophy (LVH). Moreover the analysis of influence of 4G/5G PAI and I/D ACE gene polymorphism on intensification of aforementioned alterations among hypertensive patients was performed. Research was carried out in 170 subjects under 40 years old, in two study groups, HT-- hypertensive group--125 patients with previously untreated hypertension without clinical features of ischaemic heart disease and NT--45 normotensive, healthy subjects. HT group has been further divided into four subgroups: DLP (dyslipidemic, n = 51), NLP (normolipidemic n = 74), LVH+ (with features of left ventricle hypertrophy, n = 35), LVH (-) (without features of left ventricle hypertrophy, n = 90). In a whole HT group significantly higher levels of PAI-1, t-PA and Fb were noted in comparison to NT group, considerably more pronounced within DLP rather than NLP subgroups. Moreover, pronounced increase in ACE activity was recorded in DLP and LVH+ subgroups. It has been proved that 4G/4G homozygous subjects of 4G/5G PAI-1 gene polymorphism from HT group tend to present higher levels of PAI-1 and t-PA if contrasted to 4G/4G genotype of NT group, with more distinct effect within DLP subgroup. Carriers of D allele (genotypes I/D, D/D) of I/D ACE gene polymorphism from HT group characterise with significantly higher activity of ACE in contrast to I/I genotype of HT group, with particularly marked effect in DLP and LVH+ subgroups. Basing on above mentioned results it may be concluded that essential hypertension (especially if complicated with dyslipidemia) impairs fibrinolysis, what might be related to renin-angiotensin system activation in lipid metabolism disorders. Deletion alleles of 4G/5G polymorphism (4G allele) and I/D polymorphism (D allele) in patients with hypertension independently modify fibrinolysis towards prothrombotic state with more distinct effect in dyslipidemia. Increased activity of ACE in D allele carriers may predispose to left ventricle hypertrophy.
Jastrzebska
Maria
M
Katedra Biochemii Klinicznej i Diagnostyki Laboratoryjnej Pomorskiej AM w Szczecinie. mariajas@sci.pam.szczecin.pl
Widecka
Krystyna
K
Ciechanowicz
Andrzej
A
Goracy
Iwona
I
Wesołowska
Teresa
T
Torbus-Lisiecka
Barbara
B
Foltyńska-Nowakowska
Anna
A
Naruszewicz
Marek
M
D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000235:genetics*; D005342:Fibrinolysis / Q000235:genetics; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics*; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000235:genetics; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D011044:Poland; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000097:blood
D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen; D007703:Peptidyl-Dipeptidase A; D010959:Tissue Plasminogen Activator