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The Relation Between Insulin Resistance and Hemostasis: Pleiotropic Genes and Common Environment

Published online by Cambridge University Press:  21 February 2012

Marlies de Lange ,
Harold Snieder ,
Robert A. S. Ariëns ,
Toby Andrew ,
Peter J. Grant  and
Tim D. Spector
Marlies de Lange
Affiliation:
Twin Research & Genetic Epidemiology Unit, St Thomas' Hospital, London, UK.
Harold Snieder
Affiliation:
Twin Research & Genetic Epidemiology Unit, St Thomas' Hospital, London, UK; Department of Pediatrics: Georgia Prevention Institute, Medical College Georgia, Augusta, Georgia, USA.
Robert A. S. Ariëns
Affiliation:
Academic Unit of Molecular Vascular Medicine, General Infirmary, Leeds, UK.
Toby Andrew
Affiliation:
Twin Research & Genetic Epidemiology Unit, St Thomas' Hospital, London, UK.
Peter J. Grant
Affiliation:
Academic Unit of Molecular Vascular Medicine, General Infirmary, Leeds, UK.
Tim D. Spector*
Affiliation:
Twin Research & Genetic Epidemiology Unit, St Thomas' Hospital, London, UK. [email protected]
*
*Address for correspondence: Tim D Spector, Twin Research & Genetic Epidemiology Unit, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.

Abstract

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Risk factors for coronary heart disease (CHD), including prethrombotic changes in hemostasis, cluster with the insulin resistance (IR) syndrome. The aim of the present study was to investigate to what extent the relation between IR and hemostatic risk factors is due to shared genes or environmental factors. Multivariate genetic analysis was performed using a total of 314 (107 monozygotic and 207 dizygotic) twin pairs on IR assessed by HOMA, fibrinogen, plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA), factor VIII (FVIII), von Willebrand factor (vWF) and factor XIII Bsubunit. The relationship between IR and the 6 hemostatic factors could best be explained by an independent pathway model consisting of 2 common genetic factors, one of which influenced IR and all hemostatic factors, and 3 common environmental factors, each representing the shared variance between IR and different aspects of the hemostatic system. Genetic correlations between IR and hemostatic proteins were larger than their environmental counterparts. Since IR and prethrombotic changes are features of both diabetes and CHD, the finding of one set of pleiotropic genes warrants the identification of these common pathways which may provide new avenues for treatment and prevention of both diabetes and CHD.

Type
Articles
Information
Twin Research and Human Genetics , Volume 6 , Issue 2 , 01 April 2003 , pp. 152 - 161
Copyright
Copyright © Cambridge University Press 2003