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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
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 (CL...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875438/ https://www.ncbi.nlm.nih.gov/pubmed/24386152 http://dx.doi.org/10.1371/journal.pone.0083151 |
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author | de Lange, Zelda Rijken, Dingeman C. Hoekstra, Tiny Conradie, Karin R. Jerling, Johann C. Pieters, Marlien |
author_facet | de Lange, Zelda Rijken, Dingeman C. Hoekstra, Tiny Conradie, Karin R. Jerling, Johann C. Pieters, Marlien |
author_sort | de Lange, Zelda |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3875438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38754382014-01-02 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 de Lange, Zelda Rijken, Dingeman C. Hoekstra, Tiny Conradie, Karin R. Jerling, Johann C. Pieters, Marlien PLoS One Research Article 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. Public Library of Science 2013-12-30 /pmc/articles/PMC3875438/ /pubmed/24386152 http://dx.doi.org/10.1371/journal.pone.0083151 Text en © 2013 de Lange et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article de Lange, Zelda Rijken, Dingeman C. Hoekstra, Tiny Conradie, Karin R. Jerling, Johann C. Pieters, Marlien 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875438/ https://www.ncbi.nlm.nih.gov/pubmed/24386152 http://dx.doi.org/10.1371/journal.pone.0083151 |
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