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(Circulation. 2003;107:2422.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

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

Andreas Festa, MD; Ralph D’Agostino, Jr, PhD; Steven S. Rich, PhD; Nancy S. Jenny, PhD; Russell P. Tracy, PhD; Steven M. Haffner, MD

From the Department of Medicine (A.F., S.M.H.), Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio, San Antonio, Tex; the Department of Public Health Sciences (R.D., S.S.R.), Wake Forest University School of Medicine, Winston Salem, NC; and the Laboratory for Clinical Biochemistry Research (N.S.J., R.P.T.), Department of Pathology, University of Vermont College of Medicine, Burlington, Vt.

Reprint requests to Steven M. Haffner, MD, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, MC 7873, San Antonio, TX 78228-3900. E-mail haffner{at}uthscsa.edu

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.

Key Words: epidemiology • insulin • genetics • plasminogen activator inhibitor

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