Promoter (4G/5G) plasminogen activator inhibitor-1 genotype and plasminogen activator inhibitor-1 levels in blacks, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study.
BACKGROUND
The 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene has been related to cardiovascular disease.


RESULTS
Insulin resistance was measured with a frequently sampled intravenous glucose tolerance test in the Insulin Resistance Atherosclerosis Study (IRAS), and PAI-1 4G/5G promoter genotype was established by allele-specific polymerase chain reaction amplification of genomic DNA. There were 287 subjects with the 4G/4G genotype (18.4%), 691 heterozygote subjects (44.2%), and 586 carriers of the 5G/5G genotype (37.5%). The genotype distribution was different across the 3 ethnic groups (P=0.001). PAI-1 levels were lower in blacks than in non-Hispanic whites and Hispanics and lower in non-Hispanic whites than in Hispanics (all P=0.0001). Subjects homozygous for the 4G allele had the highest plasma PAI-1, heterozygote subjects were intermediate, and 5G homozygotes had the lowest levels of PAI-1. These patterns remained unaffected by adjustments for age, gender, clinical center, glucose tolerance status, body mass index, waist, triglycerides, and insulin resistance. Multiple linear regression analyses showed that the 4G/5G genotype explained very little of the variation in PAI-1 levels (0.63% in non-Hispanic whites, 0.99% in Hispanics, and 2.37% in blacks), and interaction analyses revealed no significant differences in the relation of circulating PAI-1 levels to the 4G/5G genotype by ethnicity (P=0.4).


CONCLUSIONS
We have shown ethnic differences in the PAI-1 4G/5G polymorphism along with corresponding differences in circulating PAI-1 levels. The association of the genotype with PAI-1 levels was seen consistently among all 3 ethnic groups and was unaffected by metabolic covariates, including insulin resistance.
Festa
Andreas
A
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78228-3900, USA.
D'Agostino
Ralph
R
Rich
Steven S
SS
Jenny
Nancy S
NS
Tracy
Russell P
RP
Haffner
Steven M
SM
D001741:Black or African American; D001161:Arteriosclerosis; D044383:Black People / Q000235:genetics*; D001823:Body Composition; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005828:Genetics, Population; D005838:Genotype; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006630:Hispanic or Latino; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D044465:White People / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1