Relationships between fibrinogen, plasminogen activator inhibitor-1, and their gene polymorphisms in current smokers with essential hypertension.
BACKGROUND
To elucidate the role of some haemostatic gene polymorphisms and environmental factors, we studied fibrinogen (Fb), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA) levels with respect to Fb G455A and PAI-1 4G/5G gene polymorphisms in smokers and nonsmokers with essential hypertension.


METHODS
The study was done in 90 patients (including 30 smokers) with essential hypertension (HT) and 40 controls (including 8 smokers). Fb and PAI-1 genotypes were PCR identified. The groups did not differ significantly as to genotype frequencies.


RESULTS
When allele A455 carriers were compared, HT patients had significantly higher Fb (p=0.015) and t-PA levels (p=0.013). Comparison of 4G allele carriers (4G/4G homozygotes) revealed significantly higher Fb (p=0.045), PAI-1 (p=0.009), and t-PA levels (p=0.007) in HT patients than controls. Interactions of Fb and PAI-1 gene polymorphisms with smoking were disclosed in HT patients only. Allele A455-carrying HT smokers compared with nonsmokers had significantly higher t-PA (12.1 +/- 5.8 vs. 7.4 +/- 3.1 ng/ml; p=0.002) and tendency to higher Fb (3.36 +/- 0.74 vs. 2.95 +/- 0.70 g/l; p=0.075) levels. Higher Fb levels were disclosed in 4G/4G smokers than nonsmokers (3.31 +/- 0.81 vs. 2.84 +/- 0.85 g/l; p=0.064). Finally, in smokers, significantly higher levels of PAI-1 were found in 4G/4G (42.1 +/- 29.4 ng/ml) as compared with 4G/5G (18.6 +/- 13.7 ng/ml; p=0.025) and 5G/5G (14.4 +/- 10.8 ng/ml; p=0.044) genotypes.


CONCLUSIONS
Smoking potentiates the prothrombotic effect of allele A455 and PAI-1 4G/4G genotype in untreated essential hypertension, reflected by increased levels of haemostatic risk factors and accelerated progression of cardiovascular diseases.
Department of Clinical Biochemistry and Laboratory Diagnostics, Pomeranian Medical University, Al Powstańców Wlkp 72, 70-111 Szczecin, Poland.
Maria
M
Jastrzebska
Iwona
I
Goracy
Marek
M
Naruszewicz
D000328:Adult; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006487:Hemostasis / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology* / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator