Association of the PAI-1 4G/5G polymorphism with blood pressure in the Quebec Family Study: Interactions with adiposity, physical activity, and the ACE I/D polymorphism

Background. Blood pressure (BP) is associated with increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme (ACE). ACE and its insertion/deletion (I/D) polymorphism have been well studied for their association with BP. However, the role of the PAI-1 4G/5G polymorphism in the association between PAI-1 and BP is less clear. Furthermore, factors such as adiposity, physical activity (PA), and other genes may influence BP. Thus the aims of this study were to examine the association of the 4G/5G polymorphism with BP, and its interactions with adiposity, physical activity, and the ACE I/D polymorphism on BP.;Methods. Eight hundred and fifteen subjects from the Quebec Family Study with valid data for height, weight, body mass index (BMI); percent fat; PA levels; systolic, diastolic and mean arterial BP (SBP, DBP, MAP); and genotype were analyzed.;Results. PAI-1 4G/5G genotype was not associated with any BP variable (SBP, DBP, MAP) or hypertension. No significant interactions were found between PAI-1 genotype and BMI or PAI-1 genotype and PA for any BP variable (SBP, DBP, MAP). Overweight and obese subjects had elevated BP (SBP, DBP, MAP) regardless of genotype, whereas normal weight 4G/4G subjects had the highest mean SBP of all normal weight groups. In the lowest tertile of PA, 4G/4G subjects had the highest mean SBP of all groups. When the PAI-1 and ACE genotypes were combined, a significant gene-gene interaction resulted for DBP only. Individuals with the ACE II genotype had the highest mean DBP values across all PAI-1 genotypes.;Conclusions. Overall, these results suggest the PAI-1 4G/5G genotype is not associated with BP or hypertension in Caucasian adults (males and females). We found limited evidence for an interaction between ACE and PAI-1 genotypes on BP variables, with a significant interaction resulting for DBP only. Furthermore, the interaction of PAI-1 genotype with adiposity and PA measures were not significant for any BP variable (SBP, DBP, MAP). However, individuals with the 4G/4G genotype may have elevated SBP, especially when combined with the phenotypes of overweight/obesity and low PA. The association of PAI-1 and ACE genotypes, along with their interactions with adiposity and PA needs to be further studied in a larger sample of adults.