Environmental and genetic factors in relation to elevated circulating levels of plasminogen activator inhibitor-1 in Caucasian patients with non-insulin-dependent diabetes mellitus.
To investigate the interaction of metabolic and genetic factors in relation to PAI-1, genotype was determined at a 4G/5G polymorphism in the PAI-1 gene promoter and a Hind III RFLP of the PAI-1 gene in 189 Caucasian NIDDM patients. PAI-1 levels were equivalent in each genotype group and PAI-1 activity correlated with fasting insulin (r=0.45), triglyceride (r=0.39) body mass index (r=0.44), cholesterol (r=0.17) and glucose (r=0.15). The regression slope (B) of PAI-1 activity on triglycerides was steeper in the 4G/4G group than the other two groups: 4G/4G B = 0.91, r = 0.62; 4G/5G B = 0.36, r=0.27; 5G/5G B=0.31, r=0.29 (difference between slopes p=0.02) and the association between PAI-1 activity and glucose remained only in the 4G/4G group (r=0.35). These results confirm the association of PAI-1 levels with the features of insulin resistance and indicate that the association between PAI-1 levels and both triglyceride and glucose is influenced by genotype in the region of PAI-1 gene promoter.
Mansfield
M W
MW
Division of Medicine, School of Medicine, University of Leeds, UK.
Stickland
M H
MH
Grant
P J
PJ
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001483:Base Sequence; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D004782:Environmental Health; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1