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Thromb Haemost 2003; 89(01): 161-168
DOI: 10.1055/s-0037-1613555
Vascular Development and Vessel Remodeling
Schattauer GmbH

Insulin resistance: an atherothrombotic syndrome

The Leeds family study
Mark S. Freeman
1   Academic Unit of Molecular Vascular Medicine, University of Leeds, UK
,
Michael W. Mansfield
1   Academic Unit of Molecular Vascular Medicine, University of Leeds, UK
,
Jenny H. Barrett
2   Genetic Epidemiology Division, Imperial Cancer Research Fund Clinical Centre in Leeds, St James’s University Hospital, Leeds, UK
,
Peter J. Grant
1   Academic Unit of Molecular Vascular Medicine, University of Leeds, UK
› Author Affiliations
Further Information

Publication History

Received 10 March 2002

Accepted after resubmission 01 October 2002

Publication Date:
09 December 2017 (online)

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Summary

The insulin resistance syndrome (IRS) is a clustering of atherothrombotic traits associated with increased vascular risk. We investigated the degree to which the phenotypic correlations between these traits are due to shared genetic and environmental factors.

A multivariate genetic analysis was performed in 537 adults from 89 healthy white north European families. All traits showed significant heritability. BMI had significant genetic correlations with fasting insulin, systolic blood pressure (sBP), plasminogen activator activator inhibitor-1 (PAI-1) and fibrinogen and triglyceride. Fasting insulin had a significant genetic correlation with fibrinogen and triglyceride and Factor VII (FVII). Significant genetic correlations were shown between triglyceride and PAI-1, fibrinogen and FVII. PAI-1 and tissue plasminogen activator (t-PA) showed significant genetic correlation with sBP and with each other. Pleiotropy was demonstrated between fibrino-gen and PAI-1, t-PA and FVII. Significant environmental correlations were also demonstrated.

This study demonstrates pleiotropy between coagulation and fibrinolytic factors. Shared genetic and environmental factors influencing haemostatic, metabolic and anthropometric traits underlie the atherothrombotic nature of the IRS.

Keywords

Pleiotropy - insulin resistance - haemostasis - genetics - families
 

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