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.
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.
authors.affiliation: Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
authors.forename: Zelda
authors.initials: Z
authors.lastname: de Lange
authors.affiliation: Department of Haematology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Dingeman C
authors.initials: DC
authors.lastname: Rijken
authors.affiliation: Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa ; Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Tiny
authors.initials: T
authors.lastname: Hoekstra
authors.affiliation: Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
authors.forename: Karin R
authors.initials: KR
authors.lastname: Conradie
authors.affiliation: Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
authors.forename: Johann C
authors.initials: JC
authors.lastname: Jerling
authors.affiliation: Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
authors.forename: Marlien
authors.initials: M
authors.lastname: Pieters
mesh_terms: D044383:Black People / Q000235:genetics*; D015992:Body Mass Index; D002947:Cities; D063285:Fibrin Clot Lysis Time; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012424:Rural Population; D013019:South Africa; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D014280:Triglycerides