title: The influence of metabolic syndrome components on plasma PAI-1 concentrations is modified by the PAI-1 4G/5G genotype and ethnicity.
abstract: 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.
authors.affiliation: Department of Chemical Pathology, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, South Africa. Electronic address: nitien.naran@wits.ac.za.
authors.forename: Nitien Hira
authors.initials: NH
authors.lastname: Naran
authors.affiliation: Department of Molecular Medicine and Haematology, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nanthakumarn
authors.initials: N
authors.lastname: Chetty
authors.affiliation: Department of Chemical Pathology, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nigel John
authors.initials: NJ
authors.lastname: Crowther
mesh_terms: 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
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human