The influence of metabolic syndrome components on plasma PAI-1 concentrations is modified by the PAI-1 4G/5G genotype and ethnicity.
Coronary artery disease (CAD) is less common in African than Indian or White subjects and elevated plasminogen activator inhibitor (PAI)-1 levels may be a risk factor for CAD. Therefore, PAI-1 levels were measured in the three populations and related to the -675 PAI-1 4G/5G promoter genotype. PAI-1 levels and anthropometric variables were measured in 310 Indian, 269 White and 107 African subjects. The PAI-1 4G allele frequency was lower in the African (0.13) than Indian (0.54) or White (0.58) populations and explained the lower PAI-1 levels in African (41.5+/-25.1 versus 68.0+/-33.3 and 70.5+/-35.7 ng/ml, respectively; p<0.0001) subjects. Except for White subjects, PAI-1 levels were higher in those with metabolic syndrome or type 2 diabetes. PAI-1 genotype did not associate with either disorder. Metabolic syndrome-related factors had little influence on PAI-1 levels in White subjects but in African and Indians subjects these variables had a major influence on PAI-1 levels in those with the 5G/5G genotype but not in subjects with the 4G/4G genotype. Ethnic differences in PAI-1 levels are largely due to differences in the frequency of the 4G and 5G alleles at the -675 locus. In Indian and African, but not White populations, the ability of metabolic syndrome-related factors to influence PAI-1 levels is modulated by the -675 genotype.
Naran
Nitien Hira
NH
Department of Chemical Pathology, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, South Africa. Electronic address: nitien.naran@wits.ac.za.
Chetty
Nanthakumarn
N
Department of Molecular Medicine and Haematology, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, South Africa.
Crowther
Nigel John
NJ
Department of Chemical Pathology, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, South Africa.
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000208:ethnology / Q000235:genetics; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013019:South Africa; D044465:White People / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human