In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time

PLoS One. 2013 Dec 30;8(12):e83151. doi: 10.1371/journal.pone.0083151. eCollection 2013.

Abstract

Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Black People / genetics*
  • Body Mass Index
  • Cities
  • Fibrin Clot Lysis Time*
  • Gene Frequency
  • Genotype
  • Humans
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics
  • Rural Population
  • South Africa
  • Triglycerides / blood
  • Waist Circumference

Substances

  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • Triglycerides

Grants and funding

This work was supported by SANPAD (South Africa - Netherlands Research Programme on Alternatives in Development); South African National Research Foundation (NRF GUN numbers 2069139, FA2006040700010 and FA2006041100003. Any opinion, finding and conclusion or recommendation expressed in this material is that of the author(s) and the NRF does not accept any liability in this regard); the South African Medical Research Council; the North-West University, Potchefstroom, South Africa; and the PHRI (Population Health Research Institute), ON, Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.