Background: The PAI-1 gene promoter 4G/5G polymorphism was found to be associated with plasma PAI-1 activity in white but not yet in Chinese patients. Hypertension might exaggerate the 4G/5G genotype effect on plasma PAI-1.
Methods: The 4G/5G genotypes and plasma PAI-1 levels were determined in 565 Chinese, 211 with and 354 without hypertension to study the genotype effect and the mode of gene-environment interaction.
Results: Hypertensive patients showed significantly higher plasma PAI-1 activity (18.2 +/- 10.0 v 14.6 +/- 8.8 IU/mL, P <.001) than normotensive subjects, and also higher body mass index (BMI) and plasma triglyceride (TG), but had neither significant difference in the 4G allele frequency (0.531 v 0.549) nor in the 4G/4G genotype percentage (24.6% v 26.5%). The 4G/4G genotypic group had higher plasma PAI-1 activity (17.6 +/- 10.2 v 14.5 +/- 7.3 IU/mL, P =.027) than the 5G/5G genotypic groups, but the statistic significance was present in women (18.1 +/- 10.0 v 14.8 +/- 6.9 IU/mL, P =.025) and not in men (17.2 +/- 10.5 v 14.3 +/- 7.7 IU/mL, P =.39) after log transformation. Multiple regression analysis of all cases documented the independent effect of BMI (P =.000), plasma TG (P =.000), age (P =.006), gender (P =.046), and the PAI-1 genotype (4G/4G v 5G/5G, P =.012) on plasma PAI-1 activity. However, the significant association of 4G/4G genotypes with higher plasma PAI-1 activity was present in women (P =.004) but not in men. There was a significant difference (P =.04) on the plasma TG-PAI-1 activity correlations between the 4G/4G (r = 0.521) and 5G/5G (r = 0.117) genotypic groups of hypertensive patients.
Conclusions: The present study showed that the 4G/4G genotype was associated with elevated plasma PAI-1 activity in Chinese patients with and without hypertension. The contribution of the PAI-1 genotype seemed larger in women. In hypertensives carrying the 4G/4G genotype, higher TG was correlated with higher PAI-1, suggesting a possible contribution of gene-environmental interaction to their high risk for atherothrombotic disease.