4G/5G promoter polymorphism of plasminogen activator inhibitor-1, lipid profiles, and ischemic stroke

The 4G allele of common 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with increased PAI-1 transcription and has been proposed as a candidate genetic risk factor for thrombotic diseases. We investigated the relationship between this polymorphism and lipid profiles and stroke risk. One hundred patients with ischemic stroke and 150 age- and sex-matched control subjects were enrolled. PAI-1 genotype was determined with the use of polymerase chain reaction and restriction-length analysis. Genotype distribution in the stroke group was 40% 4G/4G, 46% 4G/5G, and 14% 5G/5G; in the control group it was 38.7% 4G/4G, 45.3% 4G/5G, and 16% 5G/5G. The allele and genotype frequencies of 4G/5G polymorphism were not different between the stroke and control groups. Control subjects who were homozygous for the 4G allele had significantly lower high-density lipoprotein (HDL) cholesterol levels than did those carrying the 5G allele (51.2 +/- 11.8 vs 58.4 +/- 15.8 mg/dL; P =.002). In the control group, regression analysis revealed a significant contribution of 4G/4G genotype to increased triglyceride (P =.042) and to decreased HDL cholesterol (P < .001) levels. Our findings suggest that PAl-1 4G/5G promoter polymorphism alone is not associated with ischemic stroke. However, this polymorphism influences lipid levels, and the underlying mechanism must be determined.