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The influence of metabolic syndrome components on plasma PAI-1 concentrations is modified by the PAI-1 4G/5G genotype and ethnicity

  • Nitien Hira Naran
    Correspondence
    Corresponding author at: Department of Chemical Pathology, National Health Laboratory Service, University of Witwatersrand Medical School, 7 York Road, Parktown 2193, Johannesburg, South Africa. Tel.: +27 11 489 8551; fax: +27 11 489 8451.
    Affiliations
    Department of Chemical Pathology, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, South Africa
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  • Nanthakumarn Chetty
    Affiliations
    Department of Molecular Medicine and Haematology, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, South Africa
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  • Nigel John Crowther
    Affiliations
    Department of Chemical Pathology, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, South Africa
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      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.

      Keywords

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