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).


CONCLUSIONS
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.
Martínez-Calatrava
María J
MJ
Department of Internal Medicine, Hospital Universitario Clínico San Carlos, Universidad Complutense de Madrid, Spain.
González-Sánchez
José L
JL
Zabena
Carina
C
Martínez-Larrad
María T
MT
Luque-Otero
Manuel
M
Serrano-Ríos
Manuel
M
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012107:Research Design; D013030:Spain / Q000453:epidemiology; D011795:Surveys and Questionnaires; D049629:Waist-Hip Ratio
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1