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

Z de Lange, Dick Rijken, T Hoekstra, KR Conradie, JC Jerling, M Pieters

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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-1(act) 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-1(act) 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-1(act), 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-1(act) or CLT but they did influence the association of other environmental factors with PAI-1(act) 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-1(act), it contributed less than 1% to the PAI-1(act) variance. (Central) obesity was the biggest contributor to PAI-1(act) variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1(act) as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1(act) and CLT.
Original languageUndefined/Unknown
JournalPLoS One (print)
Volume8
Issue number12
DOIs
Publication statusPublished - 2013

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