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

• Published in: Circulation (New York, N.Y.) Vol. 107; no. 19; pp. 2422 - 2427
• Main Authors: Festa, Andreas, D’Agostino, Ralph, Rich, Steven S., Jenny, Nancy S., Tracy, Russell P., Haffner, Steven M.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 20.05.2003; American Heart Association, Inc
• Subjects: African Americans; African Continental Ancestry Group - genetics; Arteriosclerosis; Biological and medical sciences; Body Composition; Cardiology. Vascular system; Coronary heart disease; Diabetes Mellitus - epidemiology; Diabetes Mellitus - genetics; European Continental Ancestry Group - genetics; Female; Gene Frequency; Genetic Testing; Genetics, Population; Genotype; Glucose Tolerance Test; Heart; Heterozygote; Hispanic Americans; Homozygote; Humans; Insulin Resistance - genetics; Linear Models; Male; Medical sciences; Middle Aged; Plasminogen Activator Inhibitor 1 - blood; Plasminogen Activator Inhibitor 1 - genetics; Polymorphism, Genetic; Promoter Regions, Genetic; Human; Cardiovascular disease; Genotype; Coronary heart disease; Genetic determinism; Insulin; Ethnic group; Vascular disease; Plasminogen activator inhibitor 1; Target tissue resistance; epidemiology; genetics; Atherosclerosis; Risk factor; Race; plasminogen activator inhibitor; Comparative study
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.0000066908.82782.3A

Background— The 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene has been related to cardiovascular disease. Methods and 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.