Plasminogen-activator inhibitor-1 polymorphisms are associated with obesity and fat distribution in the Qu??bec Family Study: evidence of interactions with menopause

In Brief Objective: Obesity is associated with increased plasma levels of plasminogen-activator inhibitor-1 (PAI1), the major fibrinolysis inhibitor. PAI1 levels are also increased at menopause, a condition that is associated with fat mass gain, especially in the abdominal area. Design: We hypothesized that genetic variations within PAI1 gene are related to the amount of body fat and its regional distribution. We genotyped 666 subjects of the Québec Family Study for five PAI1 gene polymorphisms. Stratified analyses were performed with analysis of covariance in men (n = 280) and women (n = 386) separately. Results: PAI1-675 4G/5G polymorphism was strongly associated with body mass index (P ≤ 0.01) and fat mass (P ≤ 0.05) in women. The PAI1-675 4G/5G promoter polymorphism and the c.43G<A (p.A15T, rs6092) variant within the exon 1 were associated with abdominal visceral fat but only in postmenopausal women (P ≤ 0.05). More specifically, homozygotes for the −675 5G and the 43A alleles had about 50% more visceral fat compared to carriers of the −675 4G allele as well as carriers of the 43G allele. No association was observed in men. Conclusion: Taken together, these results suggest that the PAI1 gene is associated with obesity and may modulate the changes in adipose tissue distribution generally observed at menopause. This study shows that PAI1 polymorphisms are associated with body mass index and fat mass in women with abdominal visceral fat only in postmenopausal women. These results suggest that the PAI1 gene may modulate adipose tissue accumulation and its distribution differentially in pre- and postmenopausal women.