Is the plasminogen activator inhibitor-1 gene a candidate gene predisposing to hypertension? Results from a population-based study in Spain.

Background: Studies in humans and mice suggest that plasminogen activator inhibitor-1 (PAI-1) might be a candidate gene for arterial hypertension. Our aims were to analyse whether the functional 4G/5G PAI-1 polymorphism represents a risk marker for the development of arterial hypertension regardless of hypertension-related metabolic variables.

Methods: Eight hundred and fifteen unrelated individuals (387 men, age 35-74 years) from a cross-sectional, population-based, epidemiological survey in the province of Segovia (Spain) were studied. Anthropometric/biochemical parameters--body mass index, waist circumference, diastolic and systolic blood pressures, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting glucose, insulin, C-reactive protein, and PAI-1 levels--were analysed. The 4G/5G PAI-1 genotypes were established by restriction fragment length polymorphism. Insulin resistance was estimated by the homeostasis model assessment. Tobacco consumption data were obtained using a standard questionnaire.

Results: The 4G/4G PAI-1 genotype was significantly associated with a high prevalence of arterial hypertension. This association remained statistically significant even after adjustment for hypertension-related metabolic variables in our population (adjusted odds ratio, 1.858; 95% confidence interval, 1.135-3.018; P = 0.013).

Conclusion: Our results show that the 4G/4G PAI-1 genotype appears to be associated with an elevated relative risk of developing arterial hypertension, regardless of PAI-1 levels and other hypertension-related factors, in a representative sample of the Spanish population.