Relationships between fibrinogen, plasminogen activator inhibitor-1, and their gene polymorphisms in current smokers with essential hypertension.

摘要

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. MATERIAL AND 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.