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


METHODS
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 Quebec 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 < or = 0.01) and fat mass (P < or = 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 < or = 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.


CONCLUSIONS
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.
Bouchard
Luigi
L
Division of Kinesiology, Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Quebec, Canada.
Mauriège
Pascale
P
Vohl
Marie-Claude
MC
Bouchard
Claude
C
Pérusse
Louis
L
D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001823:Body Composition; D015992:Body Mass Index; D015331:Cohort Studies; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011401:Promoter Regions, Genetic; D011792:Quebec; D044465:White People
D017931:DNA Primers; D017395:Plasminogen Activator Inhibitor 1