Published Online
on April 28, 2003

A more recent version of this article appeared on May 20, 2003

This Article Full Text (PDF) All Versions of this Article: 107/19/2422    most recent 01.CIR.0000066908.82782.3Av1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Festa, A. Articles by Haffner, S. M. Search for Related Content PubMed PubMed Citation Articles by Festa, A. Articles by Haffner, S. M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Related Collections Clinical genetics Epidemiology

Submitted on December 31, 2002
Accepted on February 18, 2003

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, and 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.

^* To whom correspondence should be addressed. 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

This article has been cited by other articles:

				D. French, L. H. Hamilton, L. A. Mattano Jr, H. N. Sather, M. Devidas, J. B. Nachman, and M. V. Relling A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia: a report from the Children's Oncology Group Blood, May 1, 2008; 111(9): 4496 - 4499. [Abstract] [Full Text] [PDF]

				R. R. S. Packard and P. Libby Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction Clin. Chem., January 1, 2008; 54(1): 24 - 38. [Abstract] [Full Text] [PDF]

				S. Yende, D. C. Angus, J. Ding, A. B. Newman, J. A. Kellum, R. Li, R. E. Ferrell, J. Zmuda, S. B. Kritchevsky, T. B. Harris, et al. 4G/5G Plasminogen Activator Inhibitor-1 Polymorphisms and Haplotypes Are Associated with Pneumonia Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1129 - 1137. [Abstract] [Full Text] [PDF]

				M. R. Golomb, M. Heiny, and B. P. Garg Two Cousins With Neonatal Stroke, PAI-1 4G Variant and MTHFR A1298C Mutation J Child Neurol, June 1, 2007; 22(6): 753 - 755. [Abstract] [PDF]

				E. Duggan, M. J. O'Dwyer, E. Caraher, D. Diviney, E. McGovern, D. Kelleher, R. McManus, and T. Ryan Coagulopathy After Cardiac Surgery May Be Influenced by a Functional Plasminogen Activator Inhibitor Polymorphism Anesth. Analg., June 1, 2007; 104(6): 1343 - 1347. [Abstract] [Full Text] [PDF]

				X. Zhang, X.-O. Shu, Q. Cai, Z. Ruan, Y.-T. Gao, and W. Zheng Functional plasminogen activator inhibitor-1 gene variants and breast cancer survival. Clin. Cancer Res., October 15, 2006; 12(20): 6037 - 6042. [Abstract] [Full Text] [PDF]

				K. Jood, P. Ladenvall, A. Tjarnlund-Wolf, C. Ladenvall, M. Andersson, S. Nilsson, C. Blomstrand, and C. Jern Fibrinolytic Gene Polymorphism and Ischemic Stroke Stroke, October 1, 2005; 36(10): 2077 - 2081. [Abstract] [Full Text] [PDF]

				S. Kathiresan, S. B. Gabriel, Q. Yang, A. L. Lochner, M. G. Larson, D. Levy, G. H. Tofler, J. N. Hirschhorn, and C. J. O'Donnell Comprehensive Survey of Common Genetic Variation at the Plasminogen Activator Inhibitor-1 Locus and Relations to Circulating Plasminogen Activator Inhibitor-1 Levels Circulation, September 20, 2005; 112(12): 1728 - 1735. [Abstract] [Full Text] [PDF]

				P.-G. Wiklund, L. Nilsson, S. N. Ardnor, P. Eriksson, L. Johansson, B. Stegmayr, A. Hamsten, D. Holmberg, and K. Asplund Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke: Replicated Findings in Two Nested Case-Control Studies Based on Independent Cohorts Stroke, August 1, 2005; 36(8): 1661 - 1665. [Abstract] [Full Text] [PDF]

				M. A. Albert, J. Torres, R. J. Glynn, and P. M Ridker Perspective on Selected Issues in Cardiovascular Disease Research With a Focus on Black Americans Circulation, July 13, 2004; 110(2): e7 - e12. [Full Text] [PDF]

				D. E. Lanfear, S. Marsh, S. Cresci, W. D. Shannon, J. A. Spertus, and H. L. McLeod Genotypes associated with myocardial infarction risk are more common in African Americans than in European Americans J. Am. Coll. Cardiol., July 7, 2004; 44(1): 165 - 167. [Abstract] [Full Text] [PDF]

				C Roncal, J Orbe, J.A Rodriguez, M Belzunce, O Beloqui, J Diez, and J.A Paramo Influence of the 4G/5G PAI-1 genotype on angiotensin II-stimulated human endothelial cells and in patients with hypertension Cardiovasc Res, July 1, 2004; 63(1): 176 - 185. [Abstract] [Full Text] [PDF]

				P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19. [Full Text] [PDF]

				T. Hoekstra, J. M. Geleijnse, C. Kluft, E. J. Giltay, F. J. Kok, and E. G. Schouten 4G/4G Genotype of PAI-1 Gene Is Associated With Reduced Risk of Stroke in Elderly Stroke, December 1, 2003; 34(12): 2822 - 2828. [Abstract] [Full Text] [PDF]

				N. Sattar Commentary: Documenting ethnic variations in vascular risk: where do we go from here? The British Journal of Diabetes & Vascular Disease, July 1, 2003; 3(4): 294 - 294. [PDF]